K Akashi

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi Lineage promiscuous expression of transcription factors in normal hematopoiesis
    Toshihiro Miyamoto
    Center for Cellular and Molecular Medicine, Kyushu University Hospital, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Int J Hematol 81:361-7. 2005
  2. ncbi Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival
    Yoshikane Kikushige
    Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
    J Immunol 180:7358-67. 2008
  3. pmc Identification of eosinophil lineage-committed progenitors in the murine bone marrow
    Hiromi Iwasaki
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 201:1891-7. 2005
  4. pmc Enforced granulocyte/macrophage colony-stimulating factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion
    Junko Iwasaki-Arai
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Exp Med 197:1311-22. 2003
  5. ncbi B lymphopoiesis in the thymus
    K Akashi
    Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
    J Immunol 164:5221-6. 2000
  6. ncbi Lineage promiscuity and plasticity in hematopoietic development
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Ann N Y Acad Sci 1044:125-31. 2005
  7. ncbi Cartography of hematopoietic stem cell commitment dependent upon a reporter for transcription factor activation
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 1106:76-81. 2007
  8. doi Lymphoid lineage fate decision of hematopoietic stem cells
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 1176:18-25. 2009
  9. ncbi Epstein-Barr virus-infected natural killer cell leukemia
    K Akashi
    Department of Pathology, Stanford University School of Medicine, CA 94305, USA
    Leuk Lymphoma 40:57-66. 2000
  10. ncbi Dendritic cell potentials of early lymphoid and myeloid progenitors
    M G Manz
    Department of Pathology, Stanford University School of Medicine, 279 Campus Dr, Stanford, CA 94305 5428, USA
    Blood 97:3333-41. 2001

Research Grants

Detail Information

Publications87

  1. ncbi Lineage promiscuous expression of transcription factors in normal hematopoiesis
    Toshihiro Miyamoto
    Center for Cellular and Molecular Medicine, Kyushu University Hospital, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Int J Hematol 81:361-7. 2005
    ....
  2. ncbi Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival
    Yoshikane Kikushige
    Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
    J Immunol 180:7358-67. 2008
    ....
  3. pmc Identification of eosinophil lineage-committed progenitors in the murine bone marrow
    Hiromi Iwasaki
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 201:1891-7. 2005
    ..The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils...
  4. pmc Enforced granulocyte/macrophage colony-stimulating factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion
    Junko Iwasaki-Arai
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Exp Med 197:1311-22. 2003
    ....
  5. ncbi B lymphopoiesis in the thymus
    K Akashi
    Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
    J Immunol 164:5221-6. 2000
    ..Thus, the thymus contributes to the formation of peripheral pools of B cells as well as of alphabeta and gammadelta T cells...
  6. ncbi Lineage promiscuity and plasticity in hematopoietic development
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Ann N Y Acad Sci 1044:125-31. 2005
    ....
  7. ncbi Cartography of hematopoietic stem cell commitment dependent upon a reporter for transcription factor activation
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 1106:76-81. 2007
    ..The utilization of the transcription factor expression as a functional marker might be useful to obtain cartography of the hematopoietic development at a higher resolution...
  8. doi Lymphoid lineage fate decision of hematopoietic stem cells
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 1176:18-25. 2009
    ..We here summarize the phenotype and functional properties of such progenitors and the current developmental map for the lymphoid lineage...
  9. ncbi Epstein-Barr virus-infected natural killer cell leukemia
    K Akashi
    Department of Pathology, Stanford University School of Medicine, CA 94305, USA
    Leuk Lymphoma 40:57-66. 2000
    ....
  10. ncbi Dendritic cell potentials of early lymphoid and myeloid progenitors
    M G Manz
    Department of Pathology, Stanford University School of Medicine, 279 Campus Dr, Stanford, CA 94305 5428, USA
    Blood 97:3333-41. 2001
    ..Blood. 2001;97:3333-3341)..
  11. ncbi A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
    K Akashi
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Nature 404:193-7. 2000
    ....
  12. pmc Two distinct pathways of positive selection for thymocytes
    K Akashi
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 95:2486-91. 1998
    ..In this view, positive selection on the c-Kit- path results from a salvage of cells that failed positive selection on the c-Kit+ path...
  13. ncbi Dendritic cell development from common myeloid progenitors
    M G Manz
    Department of Pathology and Developmental Biology, B261 Beckman Center, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305 5428, USA
    Ann N Y Acad Sci 938:167-73; discussion 173-4. 2001
    ..On the basis of transplantation studies, it seems likely that most of the DCs in secondary lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived...
  14. ncbi Fetal liver myelopoiesis occurs through distinct, prospectively isolatable progenitor subsets
    D Traver
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Blood 98:627-35. 2001
    ..Blood. 2001;98:627-635)..
  15. ncbi Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines
    M Kondo
    Department of Pathology, Stanford University School of Medicine, California 94305 5324, USA
    Nature 407:383-6. 2000
    ..We conclude that cytokine signalling can regulate cell-fate decisions and propose that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development...
  16. ncbi Lymphoid precursors
    K Akashi
    Departments of Pathology and Developmental Biology, Beckman Center B 261, Stanford University School of Medicine, Stanford, CA 94305, USA
    Curr Opin Immunol 12:144-50. 2000
    ..These studies may ultimately provide candidate genes involved in lineage commitment, cell death or survival, self-renewal and migratory capacities of progenitors...
  17. doi Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages
    Yojiro Arinobu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell Stem Cell 1:416-27. 2007
    ..1 primarily organizes the hematopoietic lineage fate decision to form the earliest hematopoietic branchpoint that comprises isolatable myeloerythroid and myelolymphoid progenitor populations...
  18. ncbi Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice
    K Akashi
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Cell 89:1033-41. 1997
    ..We propose cell survival signals to be the principal function of IL-7R engagement in thymic and T cell development...
  19. ncbi Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice
    M Kondo
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Immunity 7:155-62. 1997
    ..Therefore, the development of T, B, and NK cells may be influenced by distinct intracytoplasmic signaling cascades that are activated by coupling of gamma(c)-related receptors...
  20. ncbi Role of interleukin-7 in T-cell development from hematopoietic stem cells
    K Akashi
    Department of Pathology, Standford University School of Medicine 94305, USA
    Immunol Rev 165:13-28. 1998
    ..Detailed analysis of the signaling cascades activated by the IL-7R may help to reveal the differential roles of IL-7 signaling in T and B-cell development...
  21. ncbi Distal elements are critical for human CD34 expression in vivo
    Yutaka Okuno
    Hematology Oncology Division, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Blood 100:4420-6. 2002
    ..Further functional analysis of these regions in transgenic mice will be crucial for understanding CD34 gene expression in hematopoietic stem and progenitor cells...
  22. ncbi Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1
    Frank Rosenbauer
    Harvard Institutes of Medicine, Room 954, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Genet 36:624-30. 2004
    ..1 expression rescued myeloid differentiation of mutant progenitors and AML blasts. These results suggest that tightly graded reduction, rather than complete loss, of a lineage-indispensable transcription factor can induce AML...
  23. pmc Differential regulation of the human and murine CD34 genes in hematopoietic stem cells
    Yutaka Okuno
    Hematology Oncology Division, Harvard Institutes of Medicine, and Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:6246-51. 2002
    ..These data strongly support the notion that hCD34(+) human bone marrow cells contain long-term HSCs that can maintain hematopoiesis throughout life...
  24. ncbi C/EBPbeta is required for 'emergency' granulopoiesis
    Hideyo Hirai
    Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
    Nat Immunol 7:732-9. 2006
    ..C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors...
  25. pmc Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation
    Hiromi Iwasaki
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1590-600. 2005
    ..Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages...
  26. ncbi Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia
    D Traver
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Immunity 9:47-57. 1998
    ..Taken together, these data suggest that Fas has a novel role in the regulation of myelopoiesis and that Fas may act as a tumor suppressor to control leukemogenic transformation in myeloid progenitor cells...
  27. pmc AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation
    T Miyamoto
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 97:7521-6. 2000
    ....
  28. ncbi Lymphoid development from hematopoietic stem cells
    K Akashi
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Int J Hematol 69:217-26. 1999
    ..Thus, common lymphoid progenitors exist in early hematopoiesis, and expression of the IL-7R is a critical step in the initiation of lymphoid development from HSC...
  29. ncbi Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment
    Toshihiro Miyamoto
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, CA 94305, USA
    Dev Cell 3:137-47. 2002
    ..Thus, the accessibility for multiple myeloid or lymphoid programs promiscuously may allow flexibility in fate commitments at these multipotent stages...
  30. pmc Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype
    Joseph D Growney
    Division of Hematology and Department of Pathology, Brigham and Women s Hospital, 1 Blackfan Circle, Boston, MA 02115, USA
    Blood 106:494-504. 2005
    ....
  31. pmc Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis
    Yojiro Arinobu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:18105-10. 2005
    ..Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C/EBPalpha...
  32. ncbi Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1
    Frank Rosenbauer
    Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
    Nat Genet 38:27-37. 2006
    ..These results elucidate how a single transcription factor, PU.1, through the cell context-specific activity of a key cis-regulatory element, affects the development of multiple cell lineages and can induce cancer...
  33. ncbi Induction of granulocytic differentiation by 2 pathways
    Pu Zhang
    Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 99:4406-12. 2002
    ....
  34. ncbi The c-kit+ maturation pathway in mouse thymic T cell development: lineages and selection
    K Akashi
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Immunity 5:147-61. 1996
    ..Some DPhi c-kit blast cells can be salvaged to produce mature single-positive (SP) cells. DPint c-kit+ maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers...
  35. ncbi Regulation of the PU.1 gene by distal elements
    Y Li
    Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 98:2958-65. 2001
    ..1. Further analysis of this myeloid-specific regulatory element will provide insight into the regulation of this key transcriptional regulator and may be useful as a tool for targeting expression to the myeloid lineage...
  36. ncbi Identification of clonogenic common lymphoid progenitors in mouse bone marrow
    M Kondo
    Department of Pathology, Stanford University School of Medicine, California 94305, USA
    Cell 91:661-72. 1997
    ..A single Lin(-)IL-7R(+)Thy-1(-)Sca-1loc-Kit(lo) cell could generate at least both T and B cells. These data provide direct evidence for the existence of common lymphoid progenitors in sites of early hematopoiesis...
  37. ncbi Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha
    Pu Zhang
    Harvard Institutes of Medicine, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Immunity 21:853-63. 2004
    ..Therefore, C/EBP alpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity...
  38. ncbi Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis
    Steffen Koschmieder
    Department of Hematology Oncology, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 105:324-34. 2005
    ..In summary, this mouse model recapitulates many characteristics of human chronic myeloid leukemia (CML) and may help elucidate basic leukemogenic mechanisms in CML stem cells during disease initiation and progression...
  39. pmc Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 113:528-38. 2004
    ..This model system will be useful for assessing the contribution of cooperating mutations in AML and testing ras inhibitors in vivo...
  40. pmc Potential autoregulation of transcription factor PU.1 by an upstream regulatory element
    Yutaka Okuno
    Harvard Institutes of Medicine, Room 954, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Mol Cell Biol 25:2832-45. 2005
    ..These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression...
  41. ncbi Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 101:383-9. 2003
    ..These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation...
  42. pmc Single pancreatic beta cells co-express multiple islet hormone genes in mice
    H Katsuta
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
    Diabetologia 53:128-38. 2010
    ..We examined whether beta cells express other genes encoding islet hormones...
  43. pmc The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:852-64. 2009
    ....
  44. pmc Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias
    Siddhartha Jaiswal
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 100:10002-7. 2003
    ....
  45. ncbi Mouse development and cell proliferation in the absence of D-cyclins
    Katarzyna Kozar
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:477-91. 2004
    ..Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion...
  46. pmc Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes
    Ewa Sicinska
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 26:8052-60. 2006
    ..Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation...
  47. ncbi GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages
    Hiromi Iwasaki
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Immunity 19:451-62. 2003
    ..Thus, GATA-1 specifically instructs MegE commitment while excluding other fate outcomes in stem and progenitor cells, suggesting that regulation of GATA-1 is critical in maintaining multilineage homeostasis...
  48. ncbi Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome
    Claudia S Huettner
    Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 102:3363-70. 2003
    ....
  49. ncbi Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells
    Joseph T Opferman
    Howard Hughes Medical Institute, Department of Cancer Immunology and AIDS, Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA
    Science 307:1101-4. 2005
    ..Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors...
  50. pmc Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage
    Alan B Cantor
    Division of Pediatric Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    J Exp Med 205:611-24. 2008
    ..They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment...
  51. pmc Ott1(Rbm15) has pleiotropic roles in hematopoietic development
    Glen D Raffel
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 104:6001-6. 2007
    ..It is plausible that dysregulation of Ott1-dependent hematopoietic developmental pathways, in particular those affecting the megakaryocyte lineage, may contribute to OTT1-MAL-mediated leukemogenesis...
  52. ncbi Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations
    M Golam Mohi
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, NRB 1030, Boston, Massachusetts 02115, USA
    Cancer Cell 7:179-91. 2005
    ..Shp2 mutants also cause myeloproliferation in Drosophila. Mek or Tor inhibitors potently inhibit transformation, suggesting new approaches to JMML therapy...
  53. pmc Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:1708-15. 2006
    ....
  54. ncbi MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
    Brian J P Huntly
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 6:587-96. 2004
    ..These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death...
  55. ncbi Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin
    Hirokazu Shigematsu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Immunity 21:43-53. 2004
    ..These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells...
  56. ncbi Transgenic targeting with regulatory elements of the human CD34 gene
    Hanna S Radomska
    Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 100:4410-9. 2002
    ....
  57. pmc The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation
    Mark W Feinberg
    Department of Medicine, Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 26:4138-48. 2007
    ..1-/- fetal liver cells along the monocytic lineage and can activate the monocytic-specific CD14 promoter. Thus, KLF4 is a critical regulator in the transcriptional network controlling monocyte differentiation...
  58. pmc Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice
    Fumihiko Ishikawa
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney St, no 770, Boston, MA 02115, USA
    Blood 106:1565-73. 2005
    ..Thus, the NOD/SCID/IL2rgamma(null) newborn system might be an important experimental model to study the human hemato-lymphoid system...
  59. pmc Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S
    Thanyaphong Na Nakorn
    Department of Pathology and Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Clin Invest 109:1579-85. 2002
    ....
  60. pmc Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue
    Pilar Alcaide
    Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 204:431-9. 2007
    ..Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues...
  61. pmc Prospective isolation of human clonogenic common myeloid progenitors
    Markus G Manz
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 99:11872-7. 2002
    ..The isolation of highly purified hematopoietic intermediates provides tools to better understand developmental programs underlying normal and leukemic hematopoiesis...
  62. pmc Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1
    Kalindi Parmar
    Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Stem Cells 28:1186-95. 2010
    ..Collectively, our data reveal novel functions of Fancd2 and Usp1 in maintaining the bone marrow HSC compartment and suggest that FA pathway disruption may account for bone marrow failure in FA patients...
  63. ncbi Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation
    Andrew BitMansour
    Division of Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, CA, USA
    Blood 100:4660-7. 2002
    ..These results demonstrate that enhanced reconstitution of a tissue myeloid pool offers protection against lethal challenge with serious fungal and bacterial pathogens...
  64. ncbi The complex cartography of stem cell commitment
    Koichi Akashi
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 121:160-2. 2005
    ....
  65. pmc Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease
    Jing Wang
    Department of Pathology and Medicine, Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 24:368-81. 2005
    ..This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations...
  66. ncbi Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study
    K Ohtsuki
    Division of Nuclear Medicine, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
    Circulation 104:203-8. 2001
    ..The uptake of (125)I-MCP-1 correlated with the number of macrophages per unit area (r=0.85, P<0.0001). CONCLUSIONS: Radiolabeled MCP-1 may be a useful tracer for imaging monocyte/macrophage-rich experimental atherosclerotic lesions...
  67. doi Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice
    Tomoyuki Akashi
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Diabetes Metab Res Rev 24:585-90. 2008
    ..In this study, we carried out bone marrow and foetal liver cell transplantation to determine if these cells could differentiate into pancreatic beta-cells or promote regeneration...
  68. pmc Proapoptotic BID is required for myeloid homeostasis and tumor suppression
    Sandra S Zinkel
    Howard Hughes Medical Institute, Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 17:229-39. 2003
    ..Moreover, progression to CMML indicates that an upstream BH3-only molecule, BID, is required to suppress tumorigenesis...
  69. pmc Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells
    Ilona Kalaszczynska
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell 138:352-65. 2009
    ..Expression of cyclin A is particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation...
  70. pmc The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways
    Fumihiko Ishikawa
    Research Unit for Human Disease Model, Rikagaku Kenkyusho RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
    Blood 110:3591-660. 2007
    ..We propose that human DCs use unique and flexible developmental programs that cannot be categorized into the conventional myeloid or lymphoid pathway...
  71. ncbi In vivo repopulation of cytoplasmically gene transferred hematopoietic cells by temperature-sensitive mutant of recombinant Sendai viral vector
    Kumi Yoshida
    Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Biochem Biophys Res Commun 361:811-6. 2007
    ..To our knowledge, this is the first demonstration of the in vivo reconstruction of hematopoietic series by cytoplasmically gene transferred BMCs, that warrants further investigation to realize this strategy in clinical settings...
  72. ncbi Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region
    Fumihiko Ishikawa
    Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, 1 7 22 Suehiro cho Tsurumi ku, Yokohama 230 0045, Japan
    Nat Biotechnol 25:1315-21. 2007
    ..These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells...
  73. pmc The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages
    Hiromi Iwasaki
    Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan
    Genes Dev 20:3010-21. 2006
    ..We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner...
  74. ncbi Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation
    Yasuo Mori
    Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
    Eur J Haematol 79:17-24. 2007
    ..We investigated the biological and clinical significance of FLT3-ITD and/or NPM1-Mt in this context...
  75. ncbi Myeloid lineage commitment from the hematopoietic stem cell
    Hiromi Iwasaki
    Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812 8582, Japan
    Immunity 26:726-40. 2007
    ....
  76. ncbi Lineage commitment and developmental plasticity in early lymphoid progenitor subsets
    David Traver
    Dana Farber Cancer Institute, Boston Massachusetts 02115, USA
    Adv Immunol 83:1-54. 2004
  77. ncbi Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development
    Tian H Chi
    Departments of Pathology and Developmental Biology, Howard Hughes Medical Institute, Stanford University Medical School, Palo Alto, California 94305, USA
    Immunity 19:169-82. 2003
    ..Our studies indicate that BAF complexes dynamically remodel chromatin to propel sequential developmental transitions in response to external signals...
  78. pmc Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development
    Ming Yan
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:17186-91. 2004
    ..These observations suggest a previously uncharacterized mechanism of tumorigenesis, in which secondary mutation(s) in molecular events disrupting the function of a domain of the oncogene promote the development of malignancy...
  79. ncbi TEF, an antiapoptotic bZIP transcription factor related to the oncogenic E2A-HLF chimera, inhibits cell growth by down-regulating expression of the common beta chain of cytokine receptors
    Takeshi Inukai
    Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Tamaho cho, Nakakoma gun, Yamanashi 409 3898, Japan
    Blood 105:4437-44. 2005
    ..In contrast, E2A-HLF promoted cell survival more efficiently than TEF but did not down-regulate betac chain expression, suggesting that E2A-HLF retains ideal properties for driving leukemic transformation...
  80. ncbi Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo
    Akira Inoue
    Department of Experimental Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cancer Cell 2:279-88. 2002
    ..These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage...
  81. ncbi Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway
    Michael K Richards
    Division of Oncology, Department of Medicine, 660 S Euclid Ave, Campus Box 8007, Saint Louis, MO 63110
    Blood 102:3562-8. 2003
    ..Thus, regulation of G-CSF levels may provide a mechanism for directing primitive hematopoietic progenitors into the common myeloid lineage in response to environmental stresses...
  82. ncbi Thymus exclusivity: all the right conditions for T cells
    Hiromi Iwasaki
    Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan
    Immunity 25:697-700. 2006
    ..In this issue of Immunity, Laiosa et al. describe that Notch-Delta signals can protect thymic precursors from reprogramming into the myeloid lineage, antagonizing the enforced myeloid transcription factors such as PU.1 and C/EBPalpha...
  83. ncbi Distinguishable live erythroid and myeloid cells in beta-globin ECFP x lysozyme EGFP mice
    Susanne Heck
    Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Blood 101:903-6. 2003
    ..The new mouse lines should become useful tools to dissect the branching between erythroid and myelomonocytic cells during in vitro differentiation of definitive multipotent progenitors...
  84. pmc Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF
    Takahiro Maeda
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 316:860-6. 2007
    ..We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage...
  85. ncbi Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential
    Min Ye
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Immunity 19:689-99. 2003
    ..Our results demonstrate that lysozyme expression does not mark myeloid commitment and that long-term repopulation potential is maintained in primed HSCs...
  86. ncbi Unraveling the molecular components and genetic blueprints of stem cells
    Linheng Li
    Stowers Institute for Medical Research, Kansas City, MO, USA
    Biotechniques 35:1233-9. 2003
    ....
  87. ncbi [Stem cell system and regenerative medicine]
    Koichi Akashi
    Center for Cellular and Molecular Medicine, Kyushu University Hospital
    Fukuoka Igaku Zasshi 95:314-20. 2004

Research Grants10

  1. Lineage decision in blood stem and progenitor cells
    Koichi Akashi; Fiscal Year: 2007
    ..Thus, we hope these studies will help understand mechanistic effects of these transcription factors on lineage decision in normal and malignant hematopoietic development. ..
  2. Developmental Checkpoints of Murine Mast Cells
    Koichi Akashi; Fiscal Year: 2009
    ..Results obtained from this project will be critical to study mast cell biology, which eventually will help develop new therapeutic strategies for a variety of allergic and autoimmune disorders. ..