Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones1,2,3,4,5,6. An important question is whether stem cells also exhibit sex differences in physiological function and hormonal regulation in tissues that do not show sex-specific morphological differences. The terminal differentiation and function of some haematopoietic cells are regulated by sex hormones7,8,9,10, but haematopoietic stem-cell function is thought to be similar in both sexes. Here we show that mouse haematopoietic stem cells exhibit sex differences in cell-cycle regulation by oestrogen. Haematopoietic stem cells in female mice divide significantly more frequently than in male mice. This difference depends on the ovaries but not the testes. Administration of oestradiol, a hormone produced mainly in the ovaries, increased haematopoietic stem-cell division in males and females. Oestrogen levels increased during pregnancy, increasing haematopoietic stem-cell division, haematopoietic stem-cell frequency, cellularity, and erythropoiesis in the spleen. Haematopoietic stem cells expressed high levels of oestrogen receptor-α (ERα). Conditional deletion of ERα from haematopoietic stem cells reduced haematopoietic stem-cell division in female, but not male, mice and attenuated the increases in haematopoietic stem-cell division, haematopoietic stem-cell frequency, and erythropoiesis during pregnancy. Oestrogen/ERα signalling promotes haematopoietic stem-cell self-renewal, expanding splenic haematopoietic stem cells and erythropoiesis during pregnancy.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Gene Expression Omnibus
Microarray data have been deposited to the Gene Expression Omnibus under accession number GSE52711.
S.J.M. is a Howard Hughes Medical Institute Investigator and the Mary McDermott Cook Chair in Pediatric Genetics. This work was supported by the Cancer Prevention and Research Institute of Texas (awards to D.N. and S.J.M.) and the National Heart Lung and Blood Institute (HL097760 to S.J.M.). B.P.L. was supported by an Irvington Institute-Cancer Research Institute/Edmond J. Safra Memorial Fellowship. Flow-cytometry was partially supported by the National Institutes of Health (NCRR grant S10RR024574, NIAID AI036211 and NCI P30CA125123) for the BCM Cytometry and Cell Sorting Core. We also thank J. Richards, S. Mani and former members of the Nakada laboratory for discussions. This work was initiated in the Life Sciences Institute at the University of Michigan then completed at Baylor College of Medicine and Children’s Research Institute at UT Southwestern. We thank the University of Virginia Center for Research in Reproduction for measuring serum hormone levels. This work is dedicated to Nicole Ryan who passed away during the study.
Extended data figures
About this article
Frontiers in Endocrinology (2019)