The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress.
The retinoblastoma tumor suppressor protein (RB) plays important roles in the control of the cell division cycle. It is estimated that RB is dysfunctional/inactivated in up to 40% of human leukemias. The consequences of loss of RB on hematopoietic stem and progenitor cell (HSPC) function in vivo are incompletely understood. Here, we report that mice genetically deficient in Rb in all hematopoietic cells (Vav-Cre Rb knockout [KO] animals) showed altered contribution of distinct hematopoietic cell lineages to peripheral blood, bone marrow, and spleen; significantly increased extramedullary hematopoiesis in the spleen; and a 2-fold increase in the frequency of hematopoietic progenitor cells in peripheral blood. Upon competitive transplantation, HSPCs from Vav-Cre Rb KO mice contributed with an at least 4- to 6-fold less efficiency to hematopoiesis compared with control cells. HSPCs deficient in Rb presented with impaired cell-cycle exit upon stress-induced proliferation, which correlated with impaired function. In summary, Rb is critical for hematopoietic stem and progenitor cell function, localization, and differentiation.
Daria
Deidre
D
Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Department of Medicine, University of Cincinnati, OH 45229, USA.
Filippi
Marie-Dominique
MD
Knudsen
Erik S
ES
Faccio
Roberta
R
Li
Zhixiong
Z
Kalfa
Theodosia
T
Geiger
Hartmut
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002455:Cell Division; D003433:Crosses, Genetic; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D013312:Stress, Physiological
D016160:Retinoblastoma Protein