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Article: Single-cell characterization of self-renewing primary trophoblast organoids as modeling of EVT differentiation and interactions with decidual natural killer cells

TitleSingle-cell characterization of self-renewing primary trophoblast organoids as modeling of EVT differentiation and interactions with decidual natural killer cells
Authors
KeywordsExtravillous trophoblast
Placentation
Pregnancy
Trophoblast differentiation
Trophoblast organoid
Issue Date18-Oct-2023
PublisherBioMed Central
Citation
BMC Genomics, 2023, v. 24, n. 1 How to Cite?
Abstract

Background

Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are critical events for placentation. However, appropriate in vitro modelling system and regulatory programs of these two events are still lacking. Recent trophoblast organoid (TO) has advanced the molecular and mechanistic research in placentation. Here, we firstly generated the self-renewing TO from human placental villous and differentiated it into EVTs (EVT-TO) for investigating the differentiation events. We then co-cultured EVT-TO with freshly isolated decidual NKs for further study of cell communication. TO modelling of EVT differentiation as well as EVT interaction with dNK might cast new aspect for placentation research.

Results

Single-cell RNA sequencing (scRNA-seq) was applied for comprehensive characterization and molecular exploration of TOs modelling of EVT differentiation and interaction with dNKs. Multiple distinct trophoblast states and dNK subpopulations were identified, representing CTB, STB, EVT, dNK1/2/3 and dNKp. Lineage trajectory and Seurat mapping analysis identified the close resemblance of TO and EVT-TO with the human placenta characteristic. Transcription factors regulatory network analysis revealed the cell-type specific essential TFs for controlling EVT differentiation. CellphoneDB analysis predicted the ligand-receptor complexes in dNK-EVT-TO co-cultures, which relate to cytokines, immunomodulation and angiogenesis. EVT was known to affect the immune properties of dNK. Our study found out that on the other way around, dNKs could exert effects on EVT causing expression changes which are functionally important.

Conclusion

Our study documented a single-cell atlas for TO and its applications on EVT differentiation and communications with dNKs, and thus provide methodology and novel research cues for future study of human placentation.


Persistent Identifierhttp://hdl.handle.net/10722/339019
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.047
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhuang, BM-
dc.contributor.authorCao, DD-
dc.contributor.authorLi, TX-
dc.contributor.authorLiu, XF-
dc.contributor.authorLyu, MM-
dc.contributor.authorWang, SD-
dc.contributor.authorCui, XY-
dc.contributor.authorWang, L-
dc.contributor.authorChen, XL-
dc.contributor.authorLin, XL-
dc.contributor.authorLee, CL-
dc.contributor.authorChiu, PCN-
dc.contributor.authorYeung, WSB-
dc.contributor.authorYao, YQ-
dc.date.accessioned2024-03-11T10:33:14Z-
dc.date.available2024-03-11T10:33:14Z-
dc.date.issued2023-10-18-
dc.identifier.citationBMC Genomics, 2023, v. 24, n. 1-
dc.identifier.issn1471-2164-
dc.identifier.urihttp://hdl.handle.net/10722/339019-
dc.description.abstract<h3>Background</h3><p>Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are critical events for placentation. However, appropriate in vitro modelling system and regulatory programs of these two events are still lacking. Recent trophoblast organoid (TO) has advanced the molecular and mechanistic research in placentation. Here, we firstly generated the self-renewing TO from human placental villous and differentiated it into EVTs (EVT-TO) for investigating the differentiation events. We then co-cultured EVT-TO with freshly isolated decidual NKs for further study of cell communication. TO modelling of EVT differentiation as well as EVT interaction with dNK might cast new aspect for placentation research.</p><h3>Results</h3><p>Single-cell RNA sequencing (scRNA-seq) was applied for comprehensive characterization and molecular exploration of TOs modelling of EVT differentiation and interaction with dNKs. Multiple distinct trophoblast states and dNK subpopulations were identified, representing CTB, STB, EVT, dNK1/2/3 and dNKp. Lineage trajectory and Seurat mapping analysis identified the close resemblance of TO and EVT-TO with the human placenta characteristic. Transcription factors regulatory network analysis revealed the cell-type specific essential TFs for controlling EVT differentiation. CellphoneDB analysis predicted the ligand-receptor complexes in dNK-EVT-TO co-cultures, which relate to cytokines, immunomodulation and angiogenesis. EVT was known to affect the immune properties of dNK. Our study found out that on the other way around, dNKs could exert effects on EVT causing expression changes which are functionally important.</p><h3>Conclusion</h3><p>Our study documented a single-cell atlas for TO and its applications on EVT differentiation and communications with dNKs, and thus provide methodology and novel research cues for future study of human placentation.</p>-
dc.languageeng-
dc.publisherBioMed Central-
dc.relation.ispartofBMC Genomics-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectExtravillous trophoblast-
dc.subjectPlacentation-
dc.subjectPregnancy-
dc.subjectTrophoblast differentiation-
dc.subjectTrophoblast organoid-
dc.titleSingle-cell characterization of self-renewing primary trophoblast organoids as modeling of EVT differentiation and interactions with decidual natural killer cells-
dc.typeArticle-
dc.identifier.doi10.1186/s12864-023-09690-x-
dc.identifier.scopuseid_2-s2.0-85174459974-
dc.identifier.volume24-
dc.identifier.issue1-
dc.identifier.eissn1471-2164-
dc.identifier.isiWOS:001095837600001-
dc.identifier.issnl1471-2164-

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