Stem Cell Reports. 2017 Nov 7. pii: S2213-6711(17)30469-1. doi: 10.1016/j.stemcr.2017.10.014. [Epub ahead of print]
Efficient Induction of Syncytiotrophoblast Layer II Cells from Trophoblast Stem Cells by Canonical Wnt Signaling Activation.
Zhu D1, Gong X2, Miao L2, Fang J2, Zhang J3.
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Abstract
The syncytiotrophoblast layer is the most critical and prominent tissue in placenta. SynT cells are differentiated from trophoblast stem cells (TSCs) during early embryogenesis. Mouse TSCs can spontaneously differentiate into cells of mixed lineages in vitro upon withdrawal of stemness-maintaining factors. However, differentiation into defined placental cell lineages remains challenging. We report here that canonical Wnt signaling activation robustly induces expression of SynT-II lineage-specific genes Gcm1 and SynB and suppresses markers of other placental lineages. In contrast to mouse TSCs, the induced SynT-II cells are migratory. More importantly, the migration depends on hepatocyte growth factor (HGF) and the c-MET signaling axis. Furthermore, HGF-expressing cells lie adjacent to SynT-II cells in developing murine placenta, suggesting that HGF/c-MET signaling plays a critical role in SynT-II cell morphogenesis during the labyrinth branching process. The availability of SynT-II cells in vitro will facilitate molecular understanding of labyrinth layer development.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
C-met; WNT signaling; cell migration; differentiation; hepatocyte growth factor; mouse; placenta; syncytiotrophoblast layer II cell; trophoblast stem cell
PMID: 28860274 PMCID: PMC5626554 [Available on 2018-04-02] DOI: 10.1083/jcb.201705151