Cdk-inhibitors and exit from quiescence in primitive haematopoietic cell subsets
| Autor: | Richard, Steinman, Beatrice, Yaroslavskiy, Julie P, Goff, Sean M, Alber, Simon C, Watkins |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cyclin-Dependent Kinase Inhibitor p21 Stem Cell Factor Microscopy Confocal Tumor Suppressor Proteins Cell Cycle Cell Cycle Proteins Cell Separation Flow Cytometry Hematopoietic Stem Cells Cyclin-Dependent Kinases Cyclins Granulocyte Colony-Stimulating Factor Cytokines Humans Interleukin-3 Fluorouracil Cells Cultured Cyclin-Dependent Kinase Inhibitor p27 Immunosuppressive Agents |
| Zdroj: | British journal of haematology. 124(3) |
| ISSN: | 0007-1048 |
| Popis: | Prolonged quiescence of haematopoietic stem cells has been proposed to support durable haematopoiesis through clonal succession. Genetic experiments in mice have implicated the cyclin-dependent kinase inhibitor (cdki) p21Waf1 in sustaining stem cell quiescence, and the cdki p27Kip1 in inhibiting the expansion of more mature progenitor cells. The expression of these inhibitory proteins in human haematopoietic stem cell candidates has not hitherto been studied. We describe a rare subpopulation (3 x 10-7 umbilical cord mononuclear cells) of lineage-negative cells that exhibited sustained resistance over months to cytokine-induced cycling, and characterized the expression of p21Waf1 and p27Kip1 proteins in these cells. Whereas p27Kip1 was uniformly expressed in these cells, the expression of p21Waf1 in this population and in lineage-negative CD34+ cells was variable. For this rare subset of cells exhibiting prolonged quiescence, p21Waf1 may be dispensable and p27Kip1 necessary for growth arrest. |
| Databáze: | OpenAIRE |
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