Key Points• Hif-2a-dependent signaling is dispensable for steady-state multilineage hematopoiesis.• Hif-2a is not essential for HSC self-renewal.Local hypoxia in hematopoietic stem cell (HSC) niches is thought to regulate HSC functions. Hypoxia-inducible factor-1 (Hif-1) and Hif-2 are key mediators of cellular responses to hypoxia. Although oxygen-regulated a-subunits of Hifs, namely Hif-1a and Hif-2a, are closely related, they play overlapping and also distinct functions in nonhematopoietic tissues. Although Hif-1a-deficient HSCs lose their activity on serial transplantation, the role for Hif-2a in cell-autonomous HSC maintenance remains unknown. Here, we demonstrate that constitutive or inducible hematopoiesis-specific Hif-2a deletion does not affect HSC numbers and steady-state hematopoiesis. Furthermore, using serial transplantations and 5-fluorouracil treatment, we demonstrate that HSCs do not require Hif-2a to self-renew and recover after hematopoietic injury. Finally, we show that Hif-1a deletion has no major impact on steady-state maintenance of Hif2a-deficient HSCs and their ability to repopulate primary recipients, indicating that Hif-1a expression does not account for normal behavior of Hif-2a-deficient HSCs. (Blood. 2013;122(10):1741-1745

During embryo neurogenesis, neurons that originate from stem cells located in the forebrain subventricular zone (SVZ) continuously migrate to the olfactory bulb (OB). However, other authors describe the occurrence of resident stem cells in the OB. In the present work we report that the absence of tumor suppressor protein p53 increases the number of neurosphere-forming cells and the proliferation of stem cells derived from 13.5-day embryo OB. Interestingly, differentiation of p53 knockout-derived neurospheres was biased toward neuronal precursors, suggesting a role for p53 in the differentiation process. Moreover, we demonstrate the relevance of p53 in maintaining chromosomal stability in response to genotoxic insult. Finally, our data show that neurosphere stem cells are highly resistant to long-term epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) deprivation in a p53-independent fashion, and they preserve their differentiation potential. Thus, these data demonstrate that p53 controls the proliferation, chromosomal stability and differentiation pattern of embryonic mouse olfactory bulb stem cells.