The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation

被引:228
作者
Rhodes, Katrin E. [1 ]
Gekas, Christos [1 ]
Wang, Yanling [1 ]
Lux, Christopher T. [5 ]
Francis, Cameron S. [1 ]
Chan, David N. [1 ]
Conway, Simon [5 ]
Orkin, Stuart H. [6 ,7 ,8 ]
Yoder, Mervin C. [5 ]
Mikkola, Hanna K. A. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Eli Edyth Broad Ctr Regenerat Med & Stem Cell Res, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[5] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA
[6] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[7] Howard Hughes Med Inst, Boston, MA 02115 USA
[8] Harvard Stem Cell Inst, Boston, MA 02115 USA
关键词
D O I
10.1016/j.stem.2008.01.001
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myeloerythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation.
引用
收藏
页码:252 / 263
页数:12
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