Hematopoietic stem cells (the progenitor cells of the blood system) divide significantly faster in females than males, driven by the female hormone estrogen, said researchers led by those from Baylor College of Medicine in a report that appears online in the journal Nature.

“I think this changes how we think about hematopoietic stem cells and gender, and reveals a new area of biology that these stem cells are involved,” said Dr. Daisuke Nakada, assistant professor of molecular and human genetics at Baylor and a corresponding author of the report. The second corresponding author is Dr. Sean J. Morrison of the University of Texas Southwestern Medical Center in Dallas.

Hematopoietic stem cells are the progenitors from which other forms of blood cells differentiate. Nakada and others in his laboratory were looking at the rate at which hematopoietic stem cells divide. When they separated the results by the sex of the mice, they found a distinct difference.

Female stem cells divided faster

“No one had expected a sex difference in the blood system at the stem cell level,” he said. In short, the blood system stem cells in female mice divided at a higher rate than did those in males.

When they gave male and female mice estradiol (a female hormone produced mainly in the ovaries), the rate of cell division increased in both males and females. Removing the ovaries in female mice reduced the rate of hematopoietic stem cells division to that of the male. Castrating the male mice had no effect.

During pregnancy, increasing levels of estrogen in the female mice increased division of hematopoietic stem cells, their frequency and production of red blood cells in the spleen. Hematopoietic stem cells expressed high levels of estrogen receptor alpha compared to differentiated blood cells. Deleting the estrogen receptor in the hematopoietic stem cells reduced the rate of cell division in the females but not the males. During pregnancy, this deletion lowered rates of stem cell division and frequency as well as formation of red blood cells in the spleen.

“This is a totally new field,” said Nakada. While researchers have studied the system that protects the developing fetus from attack by the mother’s immune system, whether this involves hematopoietic stem cells is unclear.

Closer study

“We are going to study in more detail how estrogen and pregnancy affects hematopoietic stem cell function,” he said. This could have significance in improving hematopoietic stem cell transplantation or avoiding maternal and prenatal complications.

Others who took part in this work include: Nicole Ryan, Ayumi Kitano, Yusuke Saitoh and Makiko Takeichi, all of Baylor; Hideyuki Oguro and Morrison of UT Southwestern; and  Boaz P. Levi and George R. Wendt of the University of Michigan at Ann Arbor.

Funding for this work came from: The Cancer Prevention and Research Institute of Texas; the Howard Hughes Medical Institute; the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern; the National Heart Lung and Blood Institute (Grant HL097760); the Irvington Institute-Cancer Research Institute/Edmond J. Safra Memorial Fellowship and the National Institutes of Health (NCRR Grant S10RR024574, NIAID GrantAI036211 and NCI Grant P30CA125123) for the BCM Cytometry and Cell Sorting Core.

Nakada is a CPRIT scholar and a member of the NCI-designated Dan L. Duncan Cancer Center at Baylor.