Cell cycle control during hematopoietic cell differentiation.
This review summarizes recent studies on the cell cycle profile of hematopoietic cell differentiation and its regulatory mechanisms. Hematopoiesis involves self-renewal of stem cells, expansion of lineage-committed progenitors, and maturation into the terminal elements. The cell cycle status of each process is tightly regulated according to function: stem cells are in a quiescent state for self renewal, the immature progenitor population actively cycles for expansion, and terminally-differentiated cells are arrested in G0/G1 to efficiently express various genes. Recent investigations have defined critical components implicated in cell cycle regulation during hematopoietic cell differentiation. Inhibition of pRB phosphorylation and E2F activity, probably through the effects of negative growth factors, such as transforming growth factor-beta and the interferons, is found to be important for cell cycle arrest of stem cells. De-repression of these elements by cyclin-dependent kinases (CDKs), which can be activated by colony stimulating factors, is associated with the expansion of immature progenitor cells. Suppression of pRB phosphorylation and E2F activity is once again accompanied by terminal differentiation. Among hematopoietic cells, megakaryocytes are known to have a distinct mode of cell cycle processes, namely endomitosis, and become hyperploid. Induction of CDK inhibitor p21 and the presence of a megakaryocyte-specific licensing factor are proposed to be the underlying mechanisms of polyploidization. Further advancement in this field should help resolve many clinical problems caused by the disruption of cell cycle control of hematopoietic cells.
Furukawa
Y
Y
Department of Hematology, Jichi Medical School.
D001854:Bone Marrow Cells / Q000502:physiology; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007372:Interferons / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003115:Colony-Stimulating Factors; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D007372:Interferons; D018844:Cyclin-Dependent Kinases