Girl power: estrogen promotes hsc self-renewal

Girl Power: Estrogen Promotes HSC Self-Renewal Esther and Susan 1Immune Receptors of the Innate and Adaptive System Team, Institut d’Investigacions Biome`diques August Pi i Sunyer, Centre EstherKoplovitz, Rossello´, 149À153, 08036 Barcelona, Spain2Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA*Correspondence: Although some hematopoietic cell types are known to respond to sex hormones, hematopoietic stem cells(HSCs) are generally thought to function similarly in both sexes. Recently in Nature, show that HSCs respond to higher levels of estrogen in females, resulting in enhanced self-renewal andincreased erythropoiesis.
and increase their self-renewing divisions nificant increase in HSC and MPP cycling.
levels of estrogens in females, particularly during pregnancy, lead to sex differences diol. Alternately, increased HSC division males. HSCs do express low levels of pro- gesterone receptor (PR), but injection of in contrast, estradiol stimulates dendritic cycling is not driven by testosterone in fe- their progression to erythroid cells. This Esr1) and the more selectively expressed in erythroid cell precursors by inhibiting ERb (Esr2). Nakada et al. show that female GATA-1; however, it is possible that eryth- and male HSCs express Esr1, but not Esr2. ERa is necessary for the estradiol- more BrdU-labeled HSCs after 10 days.
ERa and use of germline Esr1-deficient correlates with increases in spleen cellu- specific estriol may promote this process.
HSC cycling to levels seen in males.
estradiol administration. Rigorous pheno- 1 week and yielding serum estradiol levels recent achievement, and this is the first subsets. One intriguing possibility is that Cell Stem Cell 14, February 6, 2014 ª2014 Elsevier Inc. 137 S.K. was supported by NIH AI92511. E.C. wassupported by a BIOTRACK postdoctoral fellow- genitors that retain long-term repopulat- Band, A.M., and Laiho, M. (2011). J. MammaryGland Biol. Neoplasia 16, 109–115.
Challen, G.A., Boles, N.C., Chambers, S.M., andGoodell, M.A. (2010). Cell Stem Cell 6, 265–278.
ability to give rise to long-term self-renew- ing HSCs upon serial transplantation.
Copley, M.R., Beer, P.A., and Eaves, C.J. (2012).
Cell Stem Cell 10, 690–697.
of TGFb have been implicated in the regu- strate if estradiol alters this property of Illing, A., Liu, P., Ostermay, S., Schilling, A., de HSCs, an earlier report showed that rela- Haan, G., Krust, A., Amling, M., Chambon, P., Schinke, T., and Tuckermann, J.P. (2012). Haema-tologica 97, 1131–1135.
in estradiol-treated mice is less quiescent and yields superior immune reconstitution Kovats, S., Carreras, E., and Agrawal, H. (2010).
Sex steroid receptors in immune cells. In SexHormones and Immunity to Infection, S.L. Klein and C.W. Roberts, eds. (New York: Springer), sooner, since their serial transplant even- Medina, K.L., Garrett, K.P., Thompson, L.F., Rossi, tually leads to reduced numbers of granu- M.I., Payne, K.J., and Kincade, P.W. (2001).
allow subsequent MEP differentiation.
Nakada, D., Oguro, H., Levi, B.P., Ryan, N., Kitano, A., Saitoh, Y., Takeichi, M., Wendt, G.R., and Morrison, S.J. (2014). Nature 505, 555–558.
Notta, F., Doulatov, S., and Dick, J.E. (2010). Blood Schuettpelz, L.G., and Link, D.C. (2013). Front Yamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K.L., Ema, H., and Nakauchi, H. (2013). Cell 154, 1112–1126.
138 Cell Stem Cell 14, February 6, 2014 ª2014 Elsevier Inc.



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