Decidual cell differentiation is evolutionarily derived from fibroblast activation

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Decidual cell differentiation in placental mammals is proposed to have evolved from wound-induced fibroblast activation, not a mesenchymal-epithelial transition, as evidenced by similarities in human endometrial fibroblast decidualization and transient myofibroblast-like cell populations.

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Abstract

What the molecular mechanisms underlying the evolutionary origin of novel cell types are is a major unresolved question in biology. The uterine decidual cell is a novel cell type of placental mammals which serves as the interface between maternal and fetal tissues during pregnancy. In this paper, we investigate two models for the nature of the differentiation of decidual cells: first, that it represents a mesenchymal-epithelial transition (MET), and second, that it evolved from wound-induced fibroblast activation (WIFA). Immunocytochemistry and RNA-seq analysis of decidualizing human endometrial fibroblasts cast doubt on the MET hypothesis and instead demonstrate a similarity between decidualization and fibroblast activation, including a central role for TGFB1. Through single-cell RNA-seq, we found a transient myofibroblast-like cell population in the in vitro differentiation trajectory of human decidual cells and found that these cells represent a pre-decidual state approaching the inferred transcriptomic transition to decidual cells. We propose an evolutionary developmental model wherein the decidual cell is a novel cell type not equivalent to the myofibroblast, but the process of decidual differentiation itself evolved as an endometrial-specific modification to fibroblast activation in response to the wound caused by embryo implantation.
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The uterine decidual cell is a novel cell type of placental mammals which serves as the interface between maternal and fetal tissues during pregnancy. In this paper, we investigate two models for the nature of the differentiation of decidual cells: first, that it represents a mesenchymal-epithelial transition (MET), and second, that it evolved from wound-induced fibroblast activation (WIFA). Immunocytochemistry and RNA-seq analysis of decidualizing human endometrial fibroblasts cast doubt on the MET hypothesis and instead demonstrate a similarity between decidualization and fibroblast activation, including a central role for TGFB1. Through single-cell RNA-seq, we found a transient myofibroblast-like cell population in the in vitro differentiation trajectory of human decidual cells and found that these cells represent a pre-decidual state approaching the inferred transcriptomic transition to decidual cells. We propose an evolutionary developmental model wherein the decidual cell is a novel cell type not equivalent to the myofibroblast, but the process of decidual differentiation itself evolved as an endometrial-specific modification to fibroblast activation in response to the wound caused by embryo implantation. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted December 21, 2020. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share Decidual cell differentiation is evolutionarily derived from fibroblast activation Longjun Wu , Daniel J Stadtmauer , Jamie Maziarz , Gunter Wagner bioRxiv 2020.12.18.423527; doi: https://doi.org/10.1101/2020.12.18.423527 Share This Article: Copy Citation Tools Decidual cell differentiation is evolutionarily derived from fibroblast activation Longjun Wu , Daniel J Stadtmauer , Jamie Maziarz , Gunter Wagner bioRxiv 2020.12.18.423527; doi: https://doi.org/10.1101/2020.12.18.423527 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Evolutionary Biology Subject Areas All Articles Animal Behavior and Cognition (7829) Biochemistry (18304) Bioengineering (14485) Bioinformatics (43308) Biophysics (22072) Cancer Biology (19181) Cell Biology (26302) Clinical Trials (138) Developmental Biology (13697) Ecology (20503) Epidemiology (2067) Evolutionary Biology (24958) Genetics (15909) Genomics (23101) Immunology (18295) Microbiology (41523) Molecular Biology (17619) Neuroscience (91310) Paleontology (683) Pathology (2926) Pharmacology and Toxicology (4973) Physiology (7917) Plant Biology (15592) Scientific Communication and Education (2073) Synthetic Biology (4449) Systems Biology (10042) Zoology (2329) window.__CF$cv$params={r:'a2255c4b0d31d89d',t:'MTc4NTI1NzE5Mg==',u:'019fa99ef13e7203aced95b0489fe89c',ut:'aYvpk6_rP4X0_Wy7z7gBOfyrn34tm6Ws7.YGe3CW24A-1785257193-1.2.1.1-rF5vSKtFzyv6G7uc0mIO_7wiidqCa3lHOmPfwHCvpkqqMpsPsla7kfgYONEO7JdceaH8kP0oBUDD8NkIwt11YXLz4oog0uvCRwI6YRStOsY',i:60};(function(){if(!document.body)return;var s=document.createElement('script');s.src='/cdn-cgi/challenge-platform/scripts/precursor/main.js';document.head.appendChild(s);})();

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