Journal Article

Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy

Kitano, Ayumi, Morrison, Sean J., Wendt, George R., Levi, Boaz P., Nakada, Daisuke, Saitoh, Yusuke, Ryan, Nicole, Oguro, Hideyuki, Takeichi, Makiko

2014

Overview

Haematopoietic stem cells are found to be regulated differently in male and female mice — haematopoietic stem cells in females divide more frequently than in males in response to oestrogen and this difference depends on the ovaries but not the testes; using a genetic approach, it is shown that the effect is dependent on expression of oestrogen receptor-α (ERα) in stem cells. Male–female difference in blood stem cells The extent to which stem cells are regulated by long-range signals versus local signals within tissues is a fundamental question in stem-cell biology. Much recent research has focused on how the stem-cell niche responds to local signals within tissues. But in conditions such as starvation or pregnancy it is likely that systemic signals will modulate stem-cell function in multiple tissues, and this study demonstrates a long-range effect of oestrogen on haematopoietic stem cells (HSCs) in pregnant mice. Using a genetic approach, the authors show that HSC stimulation, which would help the mother to meet increased haematopoietic demands, is dependent on expression of the oestrogen receptor (ERα). Hormonal levels differ in males and females but so too do the HSC cells — stem cells in female mice divide significantly more frequently than those in male mice in response to oestrogen. Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones 1 , 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 hormones 7 , 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/100 / 13/31 / 631/532/1542 / 64/110 / 64/60 / Animal development / Animals / Bone marrow / Cell Count / Cell Division - drug effects / Erythropoiesis / Estrogen / Estrogen Receptor alpha - metabolism / Estrogens / Estrogens - metabolism / Estrogens - pharmacology / Female / Females / Health aspects / Hematopoietic stem cells / Hematopoietic Stem Cells - cytology / Hematopoietic Stem Cells - drug effects / Hematopoietic Stem Cells - metabolism / Hormones / Humanities and Social Sciences / letter / Male / Mice / multidisciplinary / Ovary - drug effects / Ovary - metabolism / Physiological aspects / Pregnancy / Rodents / Science / Sex Characteristics / Signal Transduction - drug effects / Spleen - cytology / Stem cells / Transplants & implants