Abstract
Hematopoietic stem cells provide an indispensible source for replenishing the blood with all its constituents throughout the organism's lifetime. Mice with a compromised hematopoietic stem cell compartment cannot survive. p53, a major tumor suppressor gene, has been implicated in regulation of hematopoiesis. In particular, p53 plays a role in homeostasis by regulating HSC quiescence and self renewal. We recently utilized a hypomorphic p53515C allele in conjunction with Mdm2, a negative regulator of p53, to gain insights into the role of p53 in hematopoietic regulation. Our analyses revealed that p53 515C/515C Mdm2-/- double mutant mice die soon after birth due to hematopoietic failure. Further mechanistic studies revealed that in the absence of Mdm2, ROS-induced postnatal p53 activity depletes hematopoietic stem cells, progenitors and differentiated cells.
Original language | English (US) |
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Pages (from-to) | 3257-3262 |
Number of pages | 6 |
Journal | Cell Cycle |
Volume | 10 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2011 |
Keywords
- HSC
- Mdm2
- ROS
- Reactive oxygen species
- p53
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology
MD Anderson CCSG core facilities
- Research Animal Support Facility