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

Keisuke Murakami, Yie hou Lee, Emma S Lucas, Yi-Wah Chan, Ruban Peter Durairaj, Satoru Takeda, Jonathan D Moore, Bee K Tan, Siobhan Quenby, Jerry K Y Chan, Caroline Eve Gargett, Jan Joris Brosens

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48 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4542 - 4553
Number of pages12
JournalEndocrinology
Volume155
Issue number11
DOIs
Publication statusPublished - 2014

Cite this

Murakami, K., Lee, Y. H., Lucas, E. S., Chan, Y-W., Durairaj, R. P., Takeda, S., Moore, J. D., Tan, B. K., Quenby, S., Chan, J. K. Y., Gargett, C. E., & Brosens, J. J. (2014). Decidualization induces a secretome switch in perivascular niche cells of the human endometrium. Endocrinology, 155(11), 4542 - 4553. https://doi.org/10.1210/en.2014-1370