Transforming growth factor-β signaling governs the differentiation program of extravillous trophoblasts in the developing human placenta.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
12 07 2022
Historique:
entrez: 22 7 2022
pubmed: 23 7 2022
medline: 27 7 2022
Statut: ppublish

Résumé

Abnormal placentation has been noticed in a variety of pregnancy complications such as miscarriage, early-onset preeclampsia, and fetal growth restriction. Defects in the developmental program of extravillous trophoblasts (EVTs), migrating from placental anchoring villi into the maternal decidua and its vessels, is thought to be an underlying cause. Yet, key regulatory mechanisms controlling commitment and differentiation of the invasive trophoblast lineage remain largely elusive. Herein, comparative gene expression analyses of HLA-G-purified EVTs, isolated from donor-matched placenta, decidua, and trophoblast organoids (TB-ORGs), revealed biological processes and signaling pathways governing EVT development. In particular, bioinformatics analyses and manipulations in different versatile trophoblast cell models unraveled transforming growth factor-β (TGF-β) signaling as a crucial pathway driving differentiation of placental EVTs into decidual EVTs, the latter showing enrichment of a secretory gene signature. Removal of Wingless signaling and subsequent activation of the TGF-β pathway were required for the formation of human leukocyte antigen-G

Identifiants

pubmed: 35867736
doi: 10.1073/pnas.2120667119
pmc: PMC9282384
doi:

Substances chimiques

HLA-G Antigens 0
Transforming Growth Factor beta 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2120667119

Subventions

Organisme : Austrian Science Fund FWF
ID : P 31470
Pays : Austria

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Auteurs

Sandra Haider (S)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Andreas Ian Lackner (AI)

Fetal-Maternal Immunology Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Bianca Dietrich (B)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Victoria Kunihs (V)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Peter Haslinger (P)

Fetal-Maternal Immunology Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Gudrun Meinhardt (G)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Theresa Maxian (T)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Leila Saleh (L)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Christian Fiala (C)

Gynmed Clinic, 1150 Vienna, Austria.

Jürgen Pollheimer (J)

Fetal-Maternal Immunology Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

Paulina A Latos (PA)

Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria.

Martin Knöfler (M)

Placental Development Group, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, 1090 Austria.

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Classifications MeSH