cell differentiation


Summary: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

Top Publications

  1. Komatsu N, Okamoto K, Sawa S, Nakashima T, Oh Hora M, Kodama T, et al. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat Med. 2014;20:62-8 pubmed publisher
    ..These findings establish the pathological importance of Foxp3 instability in the generation of pathogenic TH17 cells in autoimmunity. ..
  2. Miskov Zivanov N, Turner M, Kane L, Morel P, Faeder J. The duration of T cell stimulation is a critical determinant of cell fate and plasticity. Sci Signal. 2013;6:ra97 pubmed publisher
    ..These results suggest that there is a critical time after TCR stimulation during which heterogeneity in the differentiating population of cells leads to increased plasticity of cell fate. ..
  3. Yoon W, Cho Y, Kim W, Bae H, Islam R, Woo K, et al. Prolyl isomerase Pin1-mediated conformational change and subnuclear focal accumulation of Runx2 are crucial for fibroblast growth factor 2 (FGF2)-induced osteoblast differentiation. J Biol Chem. 2014;289:8828-38 pubmed publisher
    ..Thus, the modulation of Pin1 activity may be a target for the regulation of bone formation. ..
  4. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7-21 pubmed publisher
    ..In this Review, we describe the function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.
  5. Tsakiridis A, Huang Y, Blin G, Skylaki S, Wymeersch F, Osorno R, et al. Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors. Development. 2014;141:1209-21 pubmed publisher
  6. Mahnke Y, Brodie T, Sallusto F, Roederer M, Lugli E. The who's who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013;43:2797-809 pubmed publisher
    ..Given that vaccine studies and adoptive cell transfer immunotherapy protocols are influenced by these recent findings, it is important to use uniform methods for identifying and discussing functionally distinct subsets of T cells. ..
  7. Kraushaar D, Zhao K. The epigenomics of embryonic stem cell differentiation. Int J Biol Sci. 2013;9:1134-44 pubmed publisher
    ..We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development. ..
  8. Zhang J, Cheng Y, Cui W, Li M, Li B, Guo L. MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol. 2014;266:56-63 pubmed publisher
    ..These findings demonstrate that miR-155 confers susceptibility to EAE by affecting inflammatory T cell responses and can be a new target for therapy of multiple sclerosis. ..
  9. Lim X, Tan S, Koh W, Chau R, Yan K, Kuo C, et al. Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science. 2013;342:1226-30 pubmed publisher

More Information


  1. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451-5 pubmed publisher
    ..enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, ..
  2. Wang H, Tibbitt M, Langer S, Leinwand L, Anseth K. Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway. Proc Natl Acad Sci U S A. 2013;110:19336-41 pubmed publisher
  3. Imayoshi I, Kageyama R. bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron. 2014;82:9-23 pubmed publisher
    ..Thus, bHLH factors play key roles in development and regeneration of the nervous system. Here, we review versatile functions of bHLH factors, focusing on telencephalic development. ..
  4. Berthoud V, Minogue P, Yu H, Schroeder R, Snabb J, Beyer E. Connexin50D47A decreases levels of fiber cell connexins and impairs lens fiber cell differentiation. Invest Ophthalmol Vis Sci. 2013;54:7614-22 pubmed publisher
    ..They also implicate Cx50 in fiber cell differentiation, since mutant lenses showed impaired degradation of organelles and decreased levels of some crystallins.
  5. Schrode N, Saiz N, Di Talia S, Hadjantonakis A. GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Dev Cell. 2014;29:454-67 pubmed publisher
    ..This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification. ..
  6. Florio M, Huttner W. Neural progenitors, neurogenesis and the evolution of the neocortex. Development. 2014;141:2182-94 pubmed publisher
    ..Here, we review the diversity of neocortical neural progenitors, their interspecies variations and their roles in determining the evolutionary increase in neuron numbers and neocortex size. ..
  7. Nei Y, Obata Ninomiya K, Tsutsui H, Ishiwata K, Miyasaka M, Matsumoto K, et al. GATA-1 regulates the generation and function of basophils. Proc Natl Acad Sci U S A. 2013;110:18620-5 pubmed publisher
    ..Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ?dblGATA mice. ..
  8. Deschene E, Myung P, Rompolas P, Zito G, Sun T, Taketo M, et al. ?-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche. Science. 2014;343:1353-6 pubmed publisher
    ..This study demonstrates a mechanism by which Wnt/?-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration. ..
  9. Kim T, Gorski S, Hahn S, Murphy K, Braciale T. Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism. Immunity. 2014;40:400-13 pubmed publisher
    ..CD24 at an elevated level, contributing to the propensity of this DC subpopulation to support CD8(+) Teff cell differentiation. Mechanistically, CD24 was shown to regulate CD8(+) T cell activation through HMGB1-mediated engagement of ..
  10. Goto Y, Panea C, Nakato G, Cebula A, Lee C, Diez M, et al. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity. 2014;40:594-607 pubmed publisher
    ..Expression of MHCII on CD11c(+) cells was necessary and sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells recognized SFB in an MHCII-dependent manner...
  11. Blondel S, Jaskowiak A, Egesipe A, Le Corf A, Navarro C, Cordette V, et al. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome. Stem Cells Transl Med. 2014;3:510-9 pubmed publisher
  12. Saba R, Wu Q, Saga Y. CYP26B1 promotes male germ cell differentiation by suppressing STRA8-dependent meiotic and STRA8-independent mitotic pathways. Dev Biol. 2014;389:173-81 pubmed publisher
    ..Taken together, we conclude that inhibition of RA is one of the essential factors to promote male germ cell differentiation, and that CYP26B1 suppresses two distinct genetic programs induced by RA: a Stra8-dependent meiotic pathway,..
  13. Dey B, Pfeifer K, Dutta A. The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev. 2014;28:491-501 pubmed publisher
    ..Therefore, the H19 long noncoding RNA has a critical trans-regulatory function in skeletal muscle differentiation and regeneration that is mediated by the microRNAs encoded within H19...
  14. Chevrier S, Emslie D, Shi W, Kratina T, Wellard C, Karnowski A, et al. The BTB-ZF transcription factor Zbtb20 is driven by Irf4 to promote plasma cell differentiation and longevity. J Exp Med. 2014;211:827-40 pubmed publisher
    ..an inhibitor of ASC differentiation, ectopic Zbtb20 expression in primary B cells facilitates terminal B cell differentiation to ASCs. In plasma cell lines, Zbtb20 induces cell survival and blocks cell cycle progression...
  15. Trifari S, Pipkin M, Bandukwala H, Aijö T, Bassein J, Chen R, et al. MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation. Proc Natl Acad Sci U S A. 2013;110:18608-13 pubmed publisher
    ..Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation. ..
  16. Ueno H, Hase K, Hashiguchi Y, Shimazaki H, Tanaka M, Miyake O, et al. Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters. Am J Surg Pathol. 2014;38:197-204 pubmed publisher
    ..40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC...
  17. Love N, Keshavan N, Lewis R, Harris W, Agathocleous M. A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation. Development. 2014;141:697-706 pubmed publisher
    ..These results suggest that an mTOR-mediated restriction point operates in vivo to couple nutrient abundance to the proliferation and differentiation programme in retinal progenitor cells. ..
  18. Yu X, Rollins D, Ruhn K, Stubblefield J, Green C, Kashiwada M, et al. TH17 cell differentiation is regulated by the circadian clock. Science. 2013;342:727-30 pubmed publisher
    ..Light-cycle disruption elevated intestinal T(H)17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control. ..
  19. Sakano D, Shiraki N, Kikawa K, Yamazoe T, Kataoka M, Umeda K, et al. VMAT2 identified as a regulator of late-stage ?-cell differentiation. Nat Chem Biol. 2014;10:141-8 pubmed publisher
    ..of this technique has been hampered by a lack of knowledge of the molecular mechanisms underlying ?-cell differentiation. The present study identified reserpine and tetrabenazine (TBZ), both vesicular monoamine transporter 2 (..
  20. Heizmann B, Kastner P, Chan S. Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals. J Exp Med. 2013;210:2823-32 pubmed publisher
    Pre-B cell receptor (pre-BCR) signaling and migration from IL-7-rich environments cooperate to drive pre-B cell differentiation via transcriptional programs that remain unclear...
  21. Huang C, Geng H, Boss I, Wang L, Melnick A. Cooperative transcriptional repression by BCL6 and BACH2 in germinal center B-cell differentiation. Blood. 2014;123:1012-20 pubmed publisher
    ..GC) B-cell fate, and are known to interact and repress transcription of PRDM1, a key driver of plasma cell differentiation. How these factors cooperate is not fully understood...
  22. John S, Russell L, Chin S, Luo W, Oshima R, Garrett Sinha L. Transcription factor Ets1, but not the closely related factor Ets2, inhibits antibody-secreting cell differentiation. Mol Cell Biol. 2014;34:522-32 pubmed publisher
    B cell differentiation into antibody-secreting cells (ASCs) is a tightly regulated process under the control of multiple transcription factors...
  23. Gong L, Ji W, Hu X, Hu W, Tang X, Huang Z, et al. Sumoylation differentially regulates Sp1 to control cell differentiation. Proc Natl Acad Sci U S A. 2014;111:5574-9 pubmed publisher
    ..Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action...
  24. Donati G, Proserpio V, Lichtenberger B, Natsuga K, Sinclair R, Fujiwara H, et al. Epidermal Wnt/β-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors. Proc Natl Acad Sci U S A. 2014;111:E1501-9 pubmed publisher
  25. Yao S, Buzo B, Pham D, Jiang L, Taparowsky E, Kaplan M, et al. Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity. 2013;39:833-45 pubmed publisher
    ..Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responses. ..
  26. Furusawa Y, Obata Y, Fukuda S, Endo T, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446-50 pubmed publisher
    ..Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut. ..
  27. Xia Y, Nivet E, Sancho Martinez I, Gallegos T, Suzuki K, Okamura D, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol. 2013;15:1507-15 pubmed publisher
    ..Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic. ..
  28. Dawlaty M, Breiling A, Le T, Barrasa M, Raddatz G, Gao Q, et al. Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell. 2014;29:102-11 pubmed publisher
    ..These findings suggest a requirement for Tet- and 5hmC-mediated DNA demethylation in proper regulation of gene expression during ESC differentiation and development...
  29. Chen Q, Zhang N, Gray R, Li H, Ewald A, Zahnow C, et al. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis. Genes Dev. 2014;28:432-7 pubmed publisher
    ..The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers. ..
  30. Treutlein B, Brownfield D, Wu A, Neff N, Mantalas G, Espinoza F, et al. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature. 2014;509:371-5 pubmed publisher
    ..This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors. ..
  31. Barresi V, Branca G, Ieni A, Reggiani Bonetti L, Baron L, Mondello S, et al. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer. Virchows Arch. 2014;464:655-62 pubmed publisher
    ..The combination of this parameter with SM invasion depth may allow identifying most of the pT1 CRC with nodal metastases. ..
  32. Lee J, Bhang D, Beede A, Huang T, Stripp B, Bloch K, et al. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell. 2014;156:440-55 pubmed publisher
    ..These findings elucidate a pathway that may be a critical target in lung diseases and provide tools to understand the mechanisms of respiratory diseases at the single-cell level. ..
  33. Yokota K, Sato K, Miyazaki T, Kitaura H, Kayama H, Miyoshi F, et al. Combination of tumor necrosis factor ? and interleukin-6 induces mouse osteoclast-like cells with bone resorption activity both in vitro and in vivo. Arthritis Rheumatol. 2014;66:121-9 pubmed publisher
  34. Yetman M, Jankowsky J. Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment. J Neurosci. 2013;33:17335-41 pubmed publisher
  35. Mendelson K, Evans T, Hla T. Sphingosine 1-phosphate signalling. Development. 2014;141:5-9 pubmed publisher
    ..Here, and in the accompanying poster, we provide an overview of S1P signalling in development and in disease. ..
  36. Yasmin N, Bauer T, Modak M, Wagner K, Schuster C, Köffel R, et al. Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. J Exp Med. 2013;210:2597-610 pubmed publisher
    ..We observed that TGF-?1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-?1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance. ..
  37. Boroviak T, Loos R, Bertone P, Smith A, Nichols J. The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification. Nat Cell Biol. 2014;16:516-28 pubmed publisher
    ..These findings suggest that formation of the epiblast coincides with competence for ERK-independent self-renewal in vitro and consequent propagation as ESC lines. ..
  38. Monticelli S. MicroRNAs in T helper cell differentiation and plasticity. Semin Immunol. 2013;25:291-8 pubmed publisher
  39. Ema H, Morita Y, Suda T. Heterogeneity and hierarchy of hematopoietic stem cells. Exp Hematol. 2014;42:74-82.e2 pubmed publisher
    ..whereas lymphoid-biased HSCs or ?/? cells overlap with ST-HSCs, suggesting that HSC lifespan is linked to cell differentiation. We also suggest that HSC heterogeneity prompts reconsideration of long-term (>4 months) multilineage ..
  40. Zhang D, Pekkanen Mattila M, Shahsavani M, Falk A, Teixeira A, Herland A. A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2014;35:1420-8 pubmed publisher
    ..We propose that the 3D in vitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease. ..
  41. Beyer T, Weiss A, Khomchuk Y, Huang K, Ogunjimi A, Varelas X, et al. Switch enhancers interpret TGF-? and Hippo signaling to control cell fate in human embryonic stem cells. Cell Rep. 2013;5:1611-24 pubmed publisher
    ..These studies define switch-enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development. ..
  42. Takasato M, Er P, Becroft M, Vanslambrouck J, Stanley E, Elefanty A, et al. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol. 2014;16:118-26 pubmed publisher
    ..Such hESC-derived components show broad renal potential ex vivo, illustrating the potential for pluripotent-stem-cell-based renal regeneration. ..
  43. Dai J, Li Y, Zhou H, Chen J, Chen M, Xiao Z. Genistein promotion of osteogenic differentiation through BMP2/SMAD5/RUNX2 signaling. Int J Biol Sci. 2013;9:1089-98 pubmed publisher
    ..Genistein enhanced osteogenic differentiation in cultured hBMSCs mainly through the BMP-dependent SMADs and RUNX2 signaling. ..
  44. Eckersley Maslin M, Thybert D, Bergmann J, Marioni J, Flicek P, Spector D. Random monoallelic gene expression increases upon embryonic stem cell differentiation. Dev Cell. 2014;28:351-65 pubmed publisher
    ..These results support a model in which random monoallelic expression occurs stochastically during differentiation and, for some genes, is compensated for by the cell to maintain the required transcriptional output of these genes. ..
  45. Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, et al. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014;344:310-3 pubmed publisher
    ..important roles in diverse biological processes; however, few have been identified that regulate immune cell differentiation and function...
  46. Bao X, He Q, Wang Y, Huang Z, Yuan Z. The roles and mechanisms of the Hippo/YAP signaling pathway in the nervous system. Yi Chuan. 2017;39:630-641 pubmed publisher
    ..In this review, we summarize the recent studies and focus on the roles and mechanisms of the Hippo/YAP signaling pathway in the nervous system, and provide insights for neural development and neural injury diseases. ..
  47. Viau S, Chabrand L, Eap S, Lorant J, Rouger K, Goudaliez F, et al. Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells. PLoS ONE. 2017;12:e0181406 pubmed publisher
    ..We demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications. ..
  48. Streltsova M, Barsov E, Erokhina S, Kovalenko E. Retroviral gene transfer into primary human NK cells activated by IL-2 and K562 feeder cells expressing membrane-bound IL-21. J Immunol Methods. 2017;450:90-94 pubmed publisher
    ..Our findings may facilitate retroviral vector-mediated genetic engineering of human primary NK cells for future immunotherapies. ..
  49. Tomov V, Palko O, Lau C, Pattekar A, Sun Y, Tacheva R, et al. Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche. Immunity. 2017;47:723-738.e5 pubmed publisher
    ..We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8+cell differentiation during chronic infection...
  50. Liu X, Zong W, Li T, Wang Y, Xu X, Zhou Z, et al. The E3 ubiquitin ligase APC/CCdh1 degrades MCPH1 after MCPH1-?TrCP2-Cdc25A-mediated mitotic entry to ensure neurogenesis. EMBO J. 2017;36:3666-3681 pubmed publisher
    ..This study provides a mechanistic understanding of how MCPH1 controls neural stem cell fate and brain development. ..
  51. Flora P, Schowalter S, Wong Deyrup S, Degennaro M, Nasrallah M, Rangan P. Transient transcriptional silencing alters the cell cycle to promote germline stem cell differentiation in Drosophila. Dev Biol. 2018;434:84-95 pubmed publisher
    ..Our results suggest that transient transcriptional silencing in the pre-cystoblast "re-programs" it away from self-renewal and toward the gamete differentiation program. ..
  52. Rao L, Qian Y, Khodabukus A, Ribar T, Bursac N. Engineering human pluripotent stem cells into a functional skeletal muscle tissue. Nat Commun. 2018;9:126 pubmed publisher
    ..iSKM bundles hold promise as a microphysiological platform for human muscle disease modeling and drug development. ..
  53. Loughran S, Comoglio F, Hamey F, Giustacchini A, Errami Y, Earp E, et al. Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program. J Exp Med. 2017;214:3085-3104 pubmed publisher
    ..Mbd3/NuRD therefore controls the fate of lymphoid progenitors, ensuring appropriate production of lineage-committed progeny and suppressing tumor formation. ..