期刊
DEVELOPMENTAL CELL
卷 27, 期 4, 页码 373-386出版社
CELL PRESS
DOI: 10.1016/j.devcel.2013.10.019
关键词
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资金
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
- Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad
- American Association of Obstetricians and Gynecologists Foundation Scholarship
- CIRM
- JCCF at UCLA
- Ruth L. Kirschstein National Research Service Award [NIH/NHLBI T32 HL69766]
- [RO1 HL097766]
The placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface. are poorly understood. We identified an Epcam(hi) labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange.
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