Stem cell repopulation efficiency but not pool size is governed by p27(kip1) - PubMed (original) (raw)
. 2000 Nov;6(11):1235-40.
doi: 10.1038/81335.
Affiliations
- PMID: 11062534
- DOI: 10.1038/81335
Stem cell repopulation efficiency but not pool size is governed by p27(kip1)
T Cheng et al. Nat Med. 2000 Nov.
Abstract
Sustained blood cell production requires preservation of a quiescent, multipotential stem cell pool that intermittently gives rise to progenitors with robust proliferative potential. The ability of cells to shift from a highly constrained to a vigorously active proliferative state is critical for maintaining stem cells while providing the responsiveness necessary for host defense. The cyclin-dependent kinase inhibitor (CDKI), p21(cip1/waf1) (p21) dominates stem cell kinetics. Here we report that another CDKI, p27(kip1) (p27), does not affect stem cell number, cell cycling, or self-renewal, but markedly alters progenitor proliferation and pool size. Therefore, distinct CDKIs govern the highly divergent stem and progenitor cell populations. When competitively transplanted, p27-deficient stem cells generate progenitors that eventually dominate blood cell production. Modulating p27 expression in a small number of stem cells may translate into effects on the majority of mature cells, thereby providing a strategy for potentiating the impact of transduced cells in stem cell gene therapy.
Similar articles
- STAT3-mediated differentiation and survival and of myeloid cells in response to granulocyte colony-stimulating factor: role for the cyclin-dependent kinase inhibitor p27(Kip1).
de Koning JP, Soede-Bobok AA, Ward AC, Schelen AM, Antonissen C, van Leeuwen D, Löwenberg B, Touw IP. de Koning JP, et al. Oncogene. 2000 Jul 6;19(29):3290-8. doi: 10.1038/sj.onc.1203627. Oncogene. 2000. PMID: 10918585 - A Limited role for p21Cip1/Waf1 in maintaining normal hematopoietic stem cell functioning.
van Os R, Kamminga LM, Ausema A, Bystrykh LV, Draijer DP, van Pelt K, Dontje B, de Haan G. van Os R, et al. Stem Cells. 2007 Apr;25(4):836-43. doi: 10.1634/stemcells.2006-0631. Epub 2006 Dec 14. Stem Cells. 2007. PMID: 17170062 - Osteoclast differentiation is associated with transient upregulation of cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and p27(KIP1).
Okahashi N, Murase Y, Koseki T, Sato T, Yamato K, Nishihara T. Okahashi N, et al. J Cell Biochem. 2001;80(3):339-45. J Cell Biochem. 2001. PMID: 11135363 - New insights into the tumor suppression function of P27(kip1).
Clurman BE, Porter P. Clurman BE, et al. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15158-60. doi: 10.1073/pnas.95.26.15158. Proc Natl Acad Sci U S A. 1998. PMID: 9860936 Free PMC article. Review. No abstract available. - Cell cycle entry of hematopoietic stem and progenitor cells controlled by distinct cyclin-dependent kinase inhibitors.
Cheng T, Scadden DT. Cheng T, et al. Int J Hematol. 2002 Jun;75(5):460-5. doi: 10.1007/BF02982107. Int J Hematol. 2002. PMID: 12095144 Review.
Cited by
- The Variation in the Traits Ameliorated by Inhibitors of JAK1/2, TGF-β, P-Selectin, and CXCR1/CXCR2 in the _Gata1_low Model Suggests That Myelofibrosis Should Be Treated by These Drugs in Combination.
Gobbo F, Martelli F, Di Virgilio A, Demaria E, Sarli G, Migliaccio AR. Gobbo F, et al. Int J Mol Sci. 2024 Jul 13;25(14):7703. doi: 10.3390/ijms25147703. Int J Mol Sci. 2024. PMID: 39062946 Free PMC article. - Loss of CDKN1B induces an age-related clonal hematopoietic disorder via Notch2 activity dysregulation.
Segatto I, Rampioni Vinciguerra GL, Pellarin I, Dall'Acqua A, Berton S, Citron F, D'Andrea S, Mungo G, Viotto D, Musco L, Di Napoli A, Aloe Spiriti MA, Canzonieri V, Gattei V, Vecchione A, Belletti B, Baldassarre G. Segatto I, et al. Cancer Commun (Lond). 2023 Jul;43(7):844-849. doi: 10.1002/cac2.12444. Epub 2023 Jun 19. Cancer Commun (Lond). 2023. PMID: 37337406 Free PMC article. No abstract available. - High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.
Heazlewood SY, Ahmad T, Cao B, Cao H, Domingues M, Sun X, Heazlewood CK, Li S, Williams B, Fulton M, White JF, Nebl T, Nefzger CM, Polo JM, Kile BT, Kraus F, Ryan MT, Sun YB, Choong PFM, Ellis SL, Anko ML, Nilsson SK. Heazlewood SY, et al. Nat Commun. 2023 Apr 13;14(1):2099. doi: 10.1038/s41467-023-37780-7. Nat Commun. 2023. PMID: 37055407 Free PMC article. - Cell-intrinsic factors governing quiescence vis-à-vis activation of adult hematopoietic stem cells.
Budgude P, Vaidya A, Kale V. Budgude P, et al. Mol Cell Biochem. 2023 Jun;478(6):1361-1382. doi: 10.1007/s11010-022-04594-y. Epub 2022 Oct 30. Mol Cell Biochem. 2023. PMID: 36309884 Review. - Cyclin-dependent kinase inhibitors in malignant hematopoiesis.
Schirripa A, Sexl V, Kollmann K. Schirripa A, et al. Front Oncol. 2022 Aug 11;12:916682. doi: 10.3389/fonc.2022.916682. eCollection 2022. Front Oncol. 2022. PMID: 36033505 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous