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The roles of p53 in hematopoietic stem cell rate

    

     At present, p53 is the star gene of the cancer studies, since more than half of cancer development and progression are reported to be related to the p53 mutation. p53 is a tumor suppressor protein, and is originally isolated as a cellular partner of simian virus 40(SV-40)-derived tumor antigens[1]. p53 has regulated several signaling pathways involved in the cell's response to stress, and plays a role in apoptosis, genomic stability, senescence, inducing cell-cycle arrest and inhibition of angiogenesis.
     Hematopoietic stem cells (HSCs) are multipotent stem cells that give rise to all the blood cell types from the myeloid and lymphoid lineages. In normal conditions, most HSCs exhibits quiescent, and only a fraction enters the cell cycle, producing progenitors of each lineage, in order to replenish the circulating blood cells. However, when stimulated by stress, lots of HSCs will enter the cell cycle and maintain their cell pool by self-renewal.
     Recent studies have revealed that p53 has been shown to play a coordination function in regulating of hematopoietic stem cell (HSC) quiescence and self-renewal. In normal hematopoiesis, p53 acts a protective function to HSCs, which is regulated by its effects on HSC quiescence, and helps to protect HSCs from DNA damage. In stress hematopoiesis, p53 can start the repair of damaged HSCs by triggering cell-cycle arrest and activating the DNA repair machinery. In addition, p53-mediated apoptosis may be involved in the physiological regulation of HSC population size and function with aging[2].
     In conclusion, p53 is a critical transcription factor that regulates signaling pathways controlling the cellular stress response, and plays a important role in the proliferation, differentiation, apoptosis, and aging of HSCs.


References
[1]. Nature 1979; 278:261–263.
[2]. J Cell Physiol 2011; 226:2215–2221.

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