Stem Cells

Gender-Specific Differences in Hematopoeisis

Science Signaling  28 Jan 2014:
Vol. 7, Issue 310, pp. ec24
DOI: 10.1126/scisignal.2005118

During pregnancy, females require increased blood volume and cells to maintain adequate circulation. Hematopoietic stem cells (HSCs) are a population of self-renewing precursor cells that reside in the bone marrow and spleen and respond to extracellular cues by undergoing proliferation and differentiation to produce blood cells. Nakada et al. found that, compared with male mice, female mice exhibited increased proliferation of HSCs without depletion of the stem cell pool, indicative of self-renewal. Ovariectomy, but not castration, eliminated the difference in HSC proliferation between males and females. Estrogen E2 administration to castrated or intact male mice or ovariectomized female mice stimulated incorporation of BrdU (a marker of cell division) into HSCs, increased the frequency of cells positive for an HSC marker, and reduced the number of cells positive for a fluorescently tagged histone, indicative of increased cell division. Whereas E2 stimulated HSC self-renewal, administration of an inhibitor of estrogen synthesis to female mice reduced HSC proliferation. Conditional knockout of the estrogen receptor alpha (ERα) from hematopoietic cells resulted in reduced incorporation of BrdU in HSCs of female, but not male, mice. Pregnant female mice with the conditional ERα knockout failed to show the increase in HSC frequency in the spleen observed in wild-type pregnant female mice. However, the increase in HSC frequency in the bone marrow was not affected, suggesting that the bone marrow responds to other systemic regulators of HSC proliferation. This study identifies a gender-specific difference in stem cell regulation and may explain some of the physiological changes associated with human pregnancy, such as enlarged spleen.

D. Nakada, H. Oguro, B. P. Levi, N. Ryan, A. Kitano, Y. Saitoh, M. Takeichi, G. R. Wendt, S. J. Morrison, Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature 505, 555–558 (2014). [PubMed]