Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.
Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones. 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, 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.
1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [2] Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Daisuke
D
Nakada
Howard Hughes Medical Institute, Department of Pediatrics, and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Hideyuki
H
Oguro
Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Boaz P
BP
Levi
1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [2].
Nicole
N
Ryan
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Ayumi
A
Kitano
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Yusuke
Y
Saitoh
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Makiko
M
Takeichi
Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
George R
GR
Wendt
Howard Hughes Medical Institute, Department of Pediatrics, and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Sean J
SJ
Morrison
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004920:Erythropoiesis; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology
D047628:Estrogen Receptor alpha; D004967:Estrogens