Cdc42

Summary

Gene Symbol: Cdc42
Description: cell division cycle 42
Alias: AI747189, AU018915, cell division control protein 42 homolog, G25K GTP-binding protein, cell division cycle 42 homolog
Species: mouse
Products:     Cdc42

Top Publications

  1. Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509-14 pubmed
  2. Corbetta S, Gualdoni S, Ciceri G, Monari M, Zuccaro E, Tybulewicz V, et al. Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB J. 2009;23:1347-57 pubmed publisher
    ..These findings show for the first time that both Rac1 and Rac3 are important for the development of the nervous system, wherein they play complementary roles during late stages of neuronal and brain development. ..
  3. García Z, Silio V, Marqués M, Cortes I, Kumar A, Hernandez C, et al. A PI3K activity-independent function of p85 regulatory subunit in control of mammalian cytokinesis. EMBO J. 2006;25:4740-51 pubmed
    ..We analyzed the mechanism by which p85alpha regulates cytokinesis; p85alpha deletion reduced Cdc42 activation in the cleavage furrow and septin 2 accumulation at this site...
  4. Beemiller P, Zhang Y, Mohan S, Levinsohn E, Gaeta I, Hoppe A, et al. A Cdc42 activation cycle coordinated by PI 3-kinase during Fc receptor-mediated phagocytosis. Mol Biol Cell. 2010;21:470-80 pubmed publisher
    ..phagocytosis by macrophages requires phosphatidylinositol 3-kinase (PI3K) and activation of the Rho-family GTPases Cdc42 and Rac1...
  5. Nishimura A, Linder M. Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding. Mol Cell Biol. 2013;33:1417-29 pubmed publisher
    ..The fidelity and variability of these CaaX processing steps are uncertain. The brain-specific splice variant of Cdc42 (bCdc42) terminates in a CCIF sequence...
  6. Causeret F, Hidalgo Sanchez M, Fort P, Backer S, Popoff M, Gauthier Rouvière C, et al. Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of precerebellar neurons toward netrin 1. Development. 2004;131:2841-52 pubmed
    ..axon outgrowth of PCN and prevents nuclei migration toward a netrin 1 source, whereas inhibition of Rac and Cdc42 sub-families impair neurite outgrowth of PCN without affecting migration...
  7. Scott R, Hawley S, Ruston J, Du J, Brakebusch C, Jones N, et al. Podocyte-specific loss of Cdc42 leads to congenital nephropathy. J Am Soc Nephrol. 2012;23:1149-54 pubmed publisher
    ..The prototypic members of this family are Cdc42, Rac1, and RhoA; these GTPases contribute to the breakdown of glomerular filtration and the resultant proteinuria, ..
  8. Choi S, Chacon Heszele M, Huang L, McKenna S, Wilson F, Zuo X, et al. Cdc42 deficiency causes ciliary abnormalities and cystic kidneys. J Am Soc Nephrol. 2013;24:1435-50 pubmed publisher
    ..In culture, the small GTPase Cdc42 co-localizes with the exocyst at primary cilia and interacts with the exocyst component Sec10...
  9. Wu X, Li S, Chrostek Grashoff A, Czuchra A, Meyer H, Yurchenco P, et al. Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. Dev Dyn. 2007;236:2767-78 pubmed
    To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs)...

More Information

Publications62

  1. Nevins A, Thurmond D. Caveolin-1 functions as a novel Cdc42 guanine nucleotide dissociation inhibitor in pancreatic beta-cells. J Biol Chem. 2006;281:18961-72 pubmed
    The cycling of the small Rho family GTPase Cdc42 is required for insulin granule exocytosis, although the regulatory proteins involved in Cdc42 cycling in pancreatic beta-cells are unknown...
  2. Florian M, Dörr K, Niebel A, Daria D, Schrezenmeier H, Rojewski M, et al. Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell. 2012;10:520-30 pubmed publisher
    ..Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs...
  3. Szczur K, Zheng Y, Filippi M. The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling. Blood. 2009;114:4527-37 pubmed publisher
    ..Using a mouse model of high Cdc42 activity, we previously demonstrated the importance of Cdc42 activity in neutrophil migration...
  4. Yang L, Wang L, Kalfa T, Cancelas J, Shang X, Pushkaran S, et al. Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis. Blood. 2007;110:3853-61 pubmed
    The Rho GTPase Cdc42 regulates adhesion, migration, and homing, as well as cell cycle progression, of hematopoietic stem cells, but its role in multilineage blood development remains unclear...
  5. Mitchell D, Bryan B, Liu J, Liu W, Zhang L, Qu J, et al. Developmental expression of three small GTPases in the mouse eye. Mol Vis. 2007;13:1144-53 pubmed
    ..To explore this possibility, we examined the expression patterns of three major Rho-GTPases: RhoA, Rac1, and Cdc42 in embryonic, postnatal (one day after birth), and adult (two-month old) mouse eye...
  6. Atwood S, Chabu C, Penkert R, Doe C, Prehoda K. Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. J Cell Sci. 2007;120:3200-6 pubmed
    b>Cdc42 recruits Par-6-aPKC to establish cell polarity from worms to mammals...
  7. Arulanandam R, Vultur A, Cao J, Carefoot E, Elliott B, Truesdell P, et al. Cadherin-cadherin engagement promotes cell survival via Rac1/Cdc42 and signal transducer and activator of transcription-3. Mol Cancer Res. 2009;7:1310-27 pubmed publisher
    ..Most importantly, our results also reveal for the first time an unexpected and dramatic surge in total Rac1 and Cdc42 protein levels triggered by cadherin engagement and an increase in Rac1 and Cdc42 activity, which is responsible ..
  8. Prakash S, Paylor R, Jenna S, Lamarche Vane N, Armstrong D, Xu B, et al. Functional analysis of ARHGAP6, a novel GTPase-activating protein for RhoA. Hum Mol Genet. 2000;9:477-88 pubmed
    ..These results suggest that ARHGAP6 has two independent functions: one as a GAP with specificity for RhoA and the other as a cytoskeletal protein that promotes actin remodeling. ..
  9. Heynen S, Tanimoto N, Joly S, Seeliger M, Samardzija M, Grimm C. Retinal degeneration modulates intracellular localization of CDC42 in photoreceptors. Mol Vis. 2011;17:2934-46 pubmed
    Rho GTPases such as RAS-related C3 botulinum substrate 1 (RAC1) and cell division cycle 42 homolog (S. cerevisiae; CDC42) have been linked to cellular processes including movement, development, and apoptosis...
  10. Park H, Cox D. Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP. Mol Biol Cell. 2009;20:4500-8 pubmed publisher
    b>Cdc42 is a key regulator of the actin cytoskeleton and activator of Wiskott-Aldrich syndrome protein (WASP)...
  11. Swiercz J, Kuner R, Behrens J, Offermanns S. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron. 2002;35:51-63 pubmed
  12. Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M, et al. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 2005;168:441-52 pubmed
    ..expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation...
  13. Bielak Zmijewska A, Kolano A, Szczepanska K, Maleszewski M, Borsuk E. Cdc42 protein acts upstream of IQGAP1 and regulates cytokinesis in mouse oocytes and embryos. Dev Biol. 2008;322:21-32 pubmed publisher
    b>Cdc42 and Rac1 Rho family GTPases, and their interacting protein IQGAP1 are the key regulators of cell polarity...
  14. Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt M. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration. Blood. 2009;113:5703-10 pubmed publisher
    ..We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin contraction are still initiated in response to chemotactic cues...
  15. Bosse T, Ehinger J, Czuchra A, Benesch S, Steffen A, Wu X, et al. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways. Mol Cell Biol. 2007;27:6615-28 pubmed
    ..c-Met ligand internalin B (InlB) were significantly impaired but not abrogated upon genetic removal of either Cdc42 or pharmacological inhibition of phosphoinositide 3-kinase (PI3-kinase)...
  16. van Hengel J, D Hooge P, Hooghe B, Wu X, Libbrecht L, De Vos R, et al. Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver. Gastroenterology. 2008;134:781-92 pubmed publisher
    The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and cell ..
  17. Cui X, Li X, Kim N. Cdc42 is implicated in polarity during meiotic resumption and blastocyst formation in the mouse. Mol Reprod Dev. 2007;74:785-94 pubmed
    Cell division cycle 42 (Cdc42), a member of the Rho family of small guanosine triphosphatase (GTPase) proteins, regulates multiple cell functions, including: motility, proliferation, apoptosis, and cell morphology...
  18. Thurnherr T, Benninger Y, Wu X, Chrostek A, Krause S, Nave K, et al. Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS. J Neurosci. 2006;26:10110-9 pubmed
    ..Ablation of Cdc42 in cells of the oligodendrocyte lineage did not affect OPC proliferation, directed migration, or in vitro ..
  19. Trollér U, Larsson C. Cdc42 is involved in PKCepsilon- and delta-induced neurite outgrowth and stress fibre dismantling. Biochem Biophys Res Commun. 2006;349:91-8 pubmed
    ..This was accompanied by stress fibre loss. Here, we have examined the role of the small GTPases, Rac1, and Cdc42, in these PKC-mediated morphological and cytoskeletal changes...
  20. Yang H, Shin M, Lee S, Kim J, Park W, Cho K, et al. Cooperative activation of PI3K by Ras and Rho family small GTPases. Mol Cell. 2012;47:281-90 pubmed publisher
    ..small GTPases activated PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities...
  21. Garvalov B, FLYNN K, Neukirchen D, Meyn L, Teusch N, Wu X, et al. Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci. 2007;27:13117-29 pubmed
    ..We analyzed the consequences of loss of Cdc42, a central regulator of polarity in multiple systems, on the polarization of mammalian neurons...
  22. Nalbant P, Hodgson L, Kraynov V, Toutchkine A, Hahn K. Activation of endogenous Cdc42 visualized in living cells. Science. 2004;305:1615-9 pubmed
    Signaling proteins are tightly regulated spatially and temporally to perform multiple functions. For Cdc42 and other guanosine triphosphatases, the subcellular location of activation is a critical determinant of cell behavior...
  23. Carè A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13:613-8 pubmed
    ..We identified specific targets of miR-133: RhoA, a GDP-GTP exchange protein regulating cardiac hypertrophy; Cdc42, a signal transduction kinase implicated in hypertrophy; and Nelf-A/WHSC2, a nuclear factor involved in ..
  24. Wan H, Liu C, Wert S, Xu W, Liao Y, Zheng Y, et al. CDC42 is required for structural patterning of the lung during development. Dev Biol. 2013;374:46-57 pubmed publisher
    ..Herein, we demonstrate that temporal-spatial regulation of epithelial cell polarity by the small GTPase, CDC42, is essential for branching morphogenesis of the developing lung...
  25. Allen W, Zicha D, Ridley A, Jones G. A role for Cdc42 in macrophage chemotaxis. J Cell Biol. 1998;141:1147-57 pubmed
    Three members of the Rho family, Cdc42, Rac, and Rho are known to regulate the organization of actin-based cytoskeletal structures. In Bac1...
  26. Maillet M, Lynch J, Sanna B, York A, Zheng Y, Molkentin J. Cdc42 is an antihypertrophic molecular switch in the mouse heart. J Clin Invest. 2009;119:3079-88 pubmed publisher
    ..Here we identify the small GTPase Cdc42 as a signaling intermediate that restrained the cardiac growth response to physiologic and pathologic stimuli...
  27. Yasuda S, Oceguera Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, et al. Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature. 2004;428:767-71 pubmed
    ..We now show that one member of this family, Cdc42, and its effector, mDia3, regulate MT attachment to kinetochores.
  28. Wang Z, Oh E, Thurmond D. Glucose-stimulated Cdc42 signaling is essential for the second phase of insulin secretion. J Biol Chem. 2007;282:9536-46 pubmed
    The small Rho family GTPases Cdc42 and Rac1 have each been shown to function in insulin exocytosis and are presumed to function in actin remodeling and insulin granule mobilization...
  29. Dehapiot B, Carriere V, Carroll J, Halet G. Polarized Cdc42 activation promotes polar body protrusion and asymmetric division in mouse oocytes. Dev Biol. 2013;377:202-12 pubmed publisher
    ..b>Cdc42 is a major player in cell polarization in many systems; however, the spatio-temporal dynamics of Cdc42 activation ..
  30. Chen L, Liao G, Yang L, Campbell K, Nakafuku M, Kuan C, et al. Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly. Proc Natl Acad Sci U S A. 2006;103:16520-5 pubmed
    ..pathway that establishes this apical-basal polarity of NE is not completely understood, but the Rho-family GTPase Cdc42 may play a critical role because it controls cadherin-based intercellular junctions and cell polarity in many ..
  31. Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz M, Maruyama M. Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. FEBS Lett. 2005;579:1039-46 pubmed
    ..Zizimin2 and zizimin1 have similar primary structures and both proteins bound and activated Cdc42 but not the Cdc42-related proteins TC10 or TCL...
  32. Chauhan B, Disanza A, Choi S, Faber S, Lou M, Beggs H, et al. Cdc42- and IRSp53-dependent contractile filopodia tether presumptive lens and retina to coordinate epithelial invagination. Development. 2009;136:3657-67 pubmed publisher
    ..Formation of filopodia is dependent on the Rho family GTPase Cdc42 and the Cdc42 effector IRSp53 (Baiap2). Loss of filopodia results in reduced lens pit invagination...
  33. Guo F, Hildeman D, Tripathi P, Velu C, Grimes H, Zheng Y. Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis. Proc Natl Acad Sci U S A. 2010;107:18505-10 pubmed publisher
    ..Here we demonstrate that T cell-specific deletion of cell-division cycle 42 (Cdc42) GTPase causes a profound loss of mature T cells...
  34. Huber C, Martensson A, Bokoch G, Nemazee D, Gavin A. FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles. J Biol Chem. 2008;283:34002-12 pubmed publisher
    ..family encode a group of critical guanine nucleotide exchange factors (GEFs), which, by specifically activating Cdc42, control cytoskeleton-dependent membrane rearrangements...
  35. Usui I, Imamura T, Huang J, Satoh H, Olefsky J. Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3-L1 adipocytes. J Biol Chem. 2003;278:13765-74 pubmed
    We investigated the role of cdc42, a Rho GTPase family member, in insulin-induced glucose transport in 3T3-L1 adipocytes...
  36. Na J, Zernicka Goetz M. Asymmetric positioning and organization of the meiotic spindle of mouse oocytes requires CDC42 function. Curr Biol. 2006;16:1249-54 pubmed
    ..Here, we show that Cdc42, a key regulator of cytoskeleton and cell polarity in other systems , is essential for meiotic maturation and ..
  37. Backer S, Hidalgo Sanchez M, Offner N, Portales Casamar E, Debant A, Fort P, et al. Trio controls the mature organization of neuronal clusters in the hindbrain. J Neurosci. 2007;27:10323-32 pubmed
    ..Altogether, those results establish a link between Trio activity, the subsequent Rac1 activation, and neuronal clusters organization, as well as a possible recruitment of the Cadherin-11 adhesive receptor to form a complex with Trio. ..
  38. Yokota Y, Eom T, Stanco A, Kim W, Rao S, Snider W, et al. Cdc42 and Gsk3 modulate the dynamics of radial glial growth, inter-radial glial interactions and polarity in the developing cerebral cortex. Development. 2010;137:4101-10 pubmed publisher
    ..Polarized expression of the cell polarity regulator Cdc42 in radial glia regulates glial endfeet activities and inter-radial glial interactions...
  39. Pleines I, Eckly A, Elvers M, Hagedorn I, Eliautou S, Bender M, et al. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood. 2010;115:3364-73 pubmed publisher
    ..Cytoskeletal reorganization is essential for platelet activation and secretion. The small GTPase Cdc42 has been implicated as an important mediator of filopodia formation and exocytosis in various cell types, but its ..
  40. Qian L, Wythe J, Liu J, Cartry J, Vogler G, Mohapatra B, et al. Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J Cell Biol. 2011;193:1181-96 pubmed publisher
    ..heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5...
  41. Melendez J, Grogg M, Zheng Y. Signaling role of Cdc42 in regulating mammalian physiology. J Biol Chem. 2011;286:2375-81 pubmed publisher
    b>Cdc42 is a member of the Rho GTPase family of intracellular molecular switches regulating multiple signaling pathways involved in actomyosin organization and cell proliferation...
  42. Yang L, Wang L, Zheng Y. Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts. Mol Biol Cell. 2006;17:4675-85 pubmed
    Recent studies in Cdc42 knockout mouse embryonic stem (ES) cells and ES-derived fibroblastoid cell lines raise concern on a body of literature derived by dominant mutant expression approach in a variety of cell lines implicating ..
  43. Schnack C, Danzer K, Hengerer B, Gillardon F. Protein array analysis of oligomerization-induced changes in alpha-synuclein protein-protein interactions points to an interference with Cdc42 effector proteins. Neuroscience. 2008;154:1450-7 pubmed publisher
    ..with recombinant alpha-synuclein oligomers lead to the identification of several GTPase activating proteins and Cdc42 effector proteins as binding partners...
  44. Konno D, Yoshimura S, Hori K, Maruoka H, Sobue K. Involvement of the phosphatidylinositol 3-kinase/rac1 and cdc42 pathways in radial migration of cortical neurons. J Biol Chem. 2005;280:5082-8 pubmed
    ..In the neocortical slice culture, a PI 3-kinase inhibitor suppressed the formation of GTP-bound Rac1 and Cdc42 and radial migration...
  45. Guo F, Velu C, Grimes H, Zheng Y. Rho GTPase Cdc42 is essential for B-lymphocyte development and activation. Blood. 2009;114:2909-16 pubmed publisher
    b>Cdc42 is a member of the Rho GTPase family that has been implicated in several cell functions including proliferation and migration, but its physiologic role needs to be dissected in each cell type...
  46. Anttonen T, Kirjavainen A, Belevich I, Laos M, Richardson W, Jokitalo E, et al. Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood. Sci Rep. 2012;2:978 pubmed publisher
    b>Cdc42 regulates the initial establishment of cytoskeletal and junctional structures, but only little is known about its role at later stages of cellular differentiation...
  47. Zheng P, Baibakov B, Wang X, Dean J. PtdIns(3,4,5)P3 is constitutively synthesized and required for spindle translocation during meiosis in mouse oocytes. J Cell Sci. 2013;126:715-21 pubmed publisher
    ..F-actin nucleator Fmn2 and Rho GTPase Cdc42 play roles in mediating the effect of PtdIns(3,4,5)P3 on F-actin assembly...
  48. Tskvitaria Fuller I, Seth A, Mistry N, Gu H, Rosen M, Wulfing C. Specific patterns of Cdc42 activity are related to distinct elements of T cell polarization. J Immunol. 2006;177:1708-20 pubmed
    ..The Rho family GTPase Cdc42 is a central regulator of cellular polarization...
  49. Aizawa R, Yamada A, Suzuki D, Iimura T, Kassai H, Harada T, et al. Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development. Mech Dev. 2012;129:38-50 pubmed publisher
    b>Cdc42, a member of the Rho subfamily of small GTPases, is known to be a regulator of multiple cellular functions, including cytoskeletal organization, cell migration, proliferation, and apoptosis...
  50. Lin Q, Yang W, Baird D, Feng Q, Cerione R. Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42. J Biol Chem. 2006;281:35253-62 pubmed
    b>Cdc42, a member of the Rho subfamily of small GTPases, influences a wide range of activities including the establishment of cell polarity, migration, and the regulation of cell growth and differentiation...
  51. Pereira J, Benninger Y, Baumann R, Gonçalves A, Ozcelik M, Thurnherr T, et al. Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system. J Cell Biol. 2009;185:147-61 pubmed publisher
    ..ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B. ..
  52. Benninger Y, Thurnherr T, Pereira J, Krause S, Wu X, Chrostek Grashoff A, et al. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development. J Cell Biol. 2007;177:1051-61 pubmed
    ..We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells...
  53. Yang L, Wang L, Geiger H, Cancelas J, Mo J, Zheng Y. Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow. Proc Natl Acad Sci U S A. 2007;104:5091-6 pubmed
    ..In a conditional-knockout mouse model, we show that Cdc42(-/-) HSCs enter the active cell cycle, resulting in significantly increased number and frequency of the stem/..