Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.

Autor:	Li Q; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: ql312@cam.ac.uk., Sharkey A; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Sheridan M; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Magistrati E; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland., Arutyunyan A; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Sanger Institute, Cambridge CB10 1SA, UK., Huhn O; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Sancho-Serra C; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Sanger Institute, Cambridge CB10 1SA, UK., Anderson H; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK., McGovern N; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Esposito L; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Fernando R; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland., Gardner L; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK., Vento-Tormo R; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Sanger Institute, Cambridge CB10 1SA, UK. Electronic address: rv4@sanger.ac.uk., Turco MY; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Electronic address: margherita.turco@fmi.ch., Moffett A; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: am485@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Feb 01; Vol. 31 (2), pp. 181-195.e9. Date of Electronic Publication: 2024 Jan 17.
DOI:	10.1016/j.stem.2023.12.013
Abstrakt:	In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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