title: Decidualization induces a secretome switch in perivascular niche cells of the human endometrium.
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.
authors.affiliation: Division of Reproductive Health, Clinical Science Research Laboratories (K.M., E.S.L., R.P.D., B.K.T., S.Q., J.J.B.), Warwick Medical School, University of Warwick, Coventry CV2 2DX, United Kingdom; Department of Obstetrics and Gynaecology (K.M., S.T.), Juntendo University Faculty of Medicine, Tokyo, 113-8421, Japan; Interdisciplinary Research Groups of BioSystems and Micromechanics, and Infectious Diseases (Y.H.L.), Singapore-MIT Alliance for Research and Technology, Singapore 138602; Warwick Systems Biology Centre (Y.-W.C., J.D.M.), University of Warwick, Coventry CV4 7AL, United Kingdom; Department of Reproductive Medicine (J.K.Y.C.), KK Women's and Children's Hospital, Singapore 229899; Cancer and Stem Cell Biology Program (J.K.Y.C.), Duke-NUS Graduate Medical School, Singapore, 169857; and The Ritchie Centre (C.E.G.), Monash Institute of Medical Research-Prince Henry's Institute, Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, 3168, Australia.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Murakami
authors.forename: Yie Hou
authors.initials: YH
authors.lastname: Lee
authors.forename: Emma S
authors.initials: ES
authors.lastname: Lucas
authors.forename: Yi-Wah
authors.initials: YW
authors.lastname: Chan
authors.forename: Ruban Peter
authors.initials: RP
authors.lastname: Durairaj
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moore
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Siobhan
authors.initials: S
authors.lastname: Quenby
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gargett
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism*; D011247:Pregnancy; D020543:Proteome / Q000378:metabolism*; D051880:Receptors, Notch / Q000502:physiology; D055153:Stem Cell Niche; D059467:Transcriptome
chemical_list: D008562:Membrane Glycoproteins; D020543:Proteome; D051880:Receptors, Notch; C582626:SUSD2 protein, human