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Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency
Single-cell RNA-seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-DeficiencyOur previous findings suggest that the fetus signals the mother when it is ready to be born through secretion of surfactant components/immune...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090199/ http://dx.doi.org/10.1210/jendso/bvab048.1532 |
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author | Chen, Jingfei Duan, Jialei Montalbano, Alina Li, Boxun Hon, Gary Mendelson, Carole R |
author_facet | Chen, Jingfei Duan, Jialei Montalbano, Alina Li, Boxun Hon, Gary Mendelson, Carole R |
author_sort | Chen, Jingfei |
collection | PubMed |
description | Single-cell RNA-seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-DeficiencyOur previous findings suggest that the fetus signals the mother when it is ready to be born through secretion of surfactant components/immune modulators, surfactant protein A (SP-A) and platelet-activating factor (PAF) by the fetal lung into amniotic fluid (AF). This occurs with increased proinflammatory cytokine expression by fetal AF macrophages (Mϕ), increased myometrial NF-κB activation and contractile (CAP) gene expression. Steroid receptor coactivator (Src)-1 and Src-2 are critical for developmental induction SP-A and PAF by the fetal lung. The finding that pregnant wild-type (WT) mice carrying Src-1 and Src-2 double-deficient fetuses (Src-1/-2(d/d)) manifested a marked delay (~38h) in parturition, further suggests that signals for parturition arise from the fetus and that Src-1 and Src-2 serve a critical role. Infiltrating leukocytes at the maternal-fetal interface (MFI)/decidua are known to play a central role in pregnancy maintenance and parturition timing. However, there is limited knowledge regarding gestational changes in immune cell composition toward term. To analyze gestational changes in the composition of immune cells within decidua and effects of Src-1/-2(d/d), we conducted single-cell RNA-seq of ~17,000 decidual leukocytes (CD45+) from pregnant mice at 15.5 and 18.5 dpc carrying WT or Src-1/-2(d/d) fetuses. Unsupervised clustering identified 22 distinct decidual immune cell clusters, comprised of Mϕ, B cells, natural killer cells, neutrophils, dendritic cells and monocytes. Significant differences in cell type composition and transcriptional profiles were found across study groups (WT @ 15.5 dpc vs. 18.5 dpc; Src-1/-2(d/d)vs. WT @15.5 dpc and 18.5 dpc). Interestingly, in deciduas of pregnant mice carrying WT fetuses, Mϕ and B cell clusters markedly increased between 15.5 and 18.5 dpc, whereas, neutrophils declined; however, these gestational changes did not occur in pregnant mice carrying Src-1/-2(d/d) fetuses. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these immune cell subtypes to uncover their putative functions. These findings highlight the complexity and dynamics of the decidual immune cell landscape during the transition from myometrial quiescence to contractility, and the fetal-maternal interactions leading to parturition. Support: NIH grants R01-HL050022 (CRM) and P01-HD087150 (CRM), Burroughs Wellcome Preterm Birth Grant #1019823 (CRM). |
format | Online Article Text |
id | pubmed-8090199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80901992021-05-06 Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency Chen, Jingfei Duan, Jialei Montalbano, Alina Li, Boxun Hon, Gary Mendelson, Carole R J Endocr Soc Reproductive Endocrinology Single-cell RNA-seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-DeficiencyOur previous findings suggest that the fetus signals the mother when it is ready to be born through secretion of surfactant components/immune modulators, surfactant protein A (SP-A) and platelet-activating factor (PAF) by the fetal lung into amniotic fluid (AF). This occurs with increased proinflammatory cytokine expression by fetal AF macrophages (Mϕ), increased myometrial NF-κB activation and contractile (CAP) gene expression. Steroid receptor coactivator (Src)-1 and Src-2 are critical for developmental induction SP-A and PAF by the fetal lung. The finding that pregnant wild-type (WT) mice carrying Src-1 and Src-2 double-deficient fetuses (Src-1/-2(d/d)) manifested a marked delay (~38h) in parturition, further suggests that signals for parturition arise from the fetus and that Src-1 and Src-2 serve a critical role. Infiltrating leukocytes at the maternal-fetal interface (MFI)/decidua are known to play a central role in pregnancy maintenance and parturition timing. However, there is limited knowledge regarding gestational changes in immune cell composition toward term. To analyze gestational changes in the composition of immune cells within decidua and effects of Src-1/-2(d/d), we conducted single-cell RNA-seq of ~17,000 decidual leukocytes (CD45+) from pregnant mice at 15.5 and 18.5 dpc carrying WT or Src-1/-2(d/d) fetuses. Unsupervised clustering identified 22 distinct decidual immune cell clusters, comprised of Mϕ, B cells, natural killer cells, neutrophils, dendritic cells and monocytes. Significant differences in cell type composition and transcriptional profiles were found across study groups (WT @ 15.5 dpc vs. 18.5 dpc; Src-1/-2(d/d)vs. WT @15.5 dpc and 18.5 dpc). Interestingly, in deciduas of pregnant mice carrying WT fetuses, Mϕ and B cell clusters markedly increased between 15.5 and 18.5 dpc, whereas, neutrophils declined; however, these gestational changes did not occur in pregnant mice carrying Src-1/-2(d/d) fetuses. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these immune cell subtypes to uncover their putative functions. These findings highlight the complexity and dynamics of the decidual immune cell landscape during the transition from myometrial quiescence to contractility, and the fetal-maternal interactions leading to parturition. Support: NIH grants R01-HL050022 (CRM) and P01-HD087150 (CRM), Burroughs Wellcome Preterm Birth Grant #1019823 (CRM). Oxford University Press 2021-05-03 /pmc/articles/PMC8090199/ http://dx.doi.org/10.1210/jendso/bvab048.1532 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Reproductive Endocrinology Chen, Jingfei Duan, Jialei Montalbano, Alina Li, Boxun Hon, Gary Mendelson, Carole R Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title | Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title_full | Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title_fullStr | Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title_full_unstemmed | Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title_short | Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency |
title_sort | single-cell rna-seq of mouse decidual leukocytes reveals intriguing gestational changes in the immune cell landscape and effects of src-1/-2 double-deficiency |
topic | Reproductive Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090199/ http://dx.doi.org/10.1210/jendso/bvab048.1532 |
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