Back to Search Start Over

CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

Authors :
Mende, Nicole
Kuchen, Erika E.
Lesche, Mathias
Grinenko, Tatyana
Kokkaliaris, Konstantinos D.
Hanenberg, Helmut
Lindemann, Dirk
Dahl, Andreas
Platz, Alexander
Höfer, Thomas
Calegari, Federico
Waskow, Claudia
Source :
The Journal of Experimental Medicine; July 2015, Vol. 212 Issue: 8 p1171-1183, 13p
Publication Year :
2015

Abstract

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis.

Details

Language :
English
ISSN :
00221007 and 15409538
Volume :
212
Issue :
8
Database :
Supplemental Index
Journal :
The Journal of Experimental Medicine
Publication Type :
Periodical
Accession number :
ejs36456231
Full Text :
https://doi.org/10.1084/jem.20150308