دورية أكاديمية
Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation.
| العنوان: | Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation. |
|---|---|
| المؤلفون: | Ackerman WE 4th; Department of Obstetrics and Gynecology and AI.Health4All Center for Health Equity Using Machine Learning and Artificial Intelligence, University of Illinois College of Medicine, Chicago, USA., Rigo MM; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., DaSilva-Arnold SC; Department of Obstetrics and Gynecology, Hackensack University Medical Center, Hackensack NJ., Do C; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., Tariq M; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., Salas M; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., Castano A; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., Zamudio S; Department of Obstetrics and Gynecology, Hackensack University Medical Center, Hackensack NJ., Tycko B; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ., Illsley NP; Department of Obstetrics and Gynecology, Hackensack University Medical Center, Hackensack NJ. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 04. Date of Electronic Publication: 2024 Jul 04. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both first trimester differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to two major placental pathologies, preeclampsia and placenta accreta spectrum, so characterization of the corresponding normal processes is crucial. In this report, our gene expression analysis, using purified human CTB and EVT cells, highlights an epithelial-mesenchymal transition (EMT) mechanism underlying CTB-EVT differentiation and provides a trophoblast-specific EMT signature. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. However, a small subgroup of genes undergoes gains of methylation (GOM) in their regulatory regions or gene bodies, associated with differential mRNA expression (DE). Prominent in this GOM-DE group are genes involved in the EMT, including multiple canonical EMT markers and the EMT-linked transcription factor RUNX1 , for which we demonstrate a functional role in modulating the migratory and invasive capacities of JEG3 trophoblast cells. This analysis of DE associated with locus-specific GOM, together with functional studies of an important GOM-DE gene, highlights epigenetically regulated genes and pathways acting in human EVT differentiation and invasion, with implications for obstetric disorders in which these processes are dysregulated. Competing Interests: Competing interests All authors assert that they have no competing interests to declare |
| معلومات مُعتمدة: | R01 HD090180 United States HD NICHD NIH HHS; U01 HD087209 United States HD NICHD NIH HHS |
| فهرسة مساهمة: | Keywords: Trophoblast; differentiation; epithelial-mesenchymal transition; methylation |
| تواريخ الأحداث: | Date Created: 20240715 Latest Revision: 20240722 |
| رمز التحديث: | 20240722 |
| مُعرف محوري في PubMed: | PMC11244995 |
| DOI: | 10.1101/2024.07.02.601748 |
| PMID: | 39005325 |
| قاعدة البيانات: | MEDLINE |
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