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Decidualization induces a secretome switch in perivascular niche cells of the human endometrium

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Murakami, Keisuke, Lee, Yie Hou, Lucas, Emma S., Chan, Yi-Wah, Peter Durairaj, Ruban Rex, Takeda, Satoru, Moore, Jonathan D., Tan, Bee K., Quenby, Siobhan, Chan, Jerry K. Y., Gargett, Caroline E. and Brosens, Jan J. (2014) Decidualization induces a secretome switch in perivascular niche cells of the human endometrium. Endocrinology, Volume 155 (Number 11). pp. 4542-4553. doi:10.1210/en.2014-1370 ISSN 0013-7227.

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Official URL: http://dx.doi.org/10.1210/en.2014-1370

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Abstract

The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and nonperivascular (W5C5−) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+:W5C5− cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared with their W5C5− counterparts. This divergence in secretomes was switched and became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of chemokines and cytokines, including leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings suggest that the decidual response is spatially organized at the embryo-maternal interface with differentiating perivascular cells establishing distinct cytokine and chemokine profiles that could potentially direct trophoblast toward maternal vessels and govern local immune responses in pregnancy.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Endocrinology
Publisher: Endocrine Society
ISSN: 0013-7227
Official Date: 12 August 2014
Dates:
DateEvent
12 August 2014Published
6 August 2014Accepted
7 May 2014Submitted
Volume: Volume 155
Number: Number 11
Page Range: pp. 4542-4553
DOI: 10.1210/en.2014-1370
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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