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

Autor: Zhuang BM; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China.; Medical school of Chinese People's Liberation Army, Chinese People's Liberation Army General Hospital, Beijing, China., Cao DD; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China. caodd@hku-szh.org., Li TX; Geneplus-Shenzhen Institute, Shenzhen, China., Liu XF; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China., Lyu MM; Department of Clinical-Translational and Basic Research Laboratory, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Shenzhen, Futian District, Guangdong, P.R. China., Wang SD; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China.; Medical school of Chinese People's Liberation Army, Chinese People's Liberation Army General Hospital, Beijing, China., Cui XY; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China., Wang L; Department of Obstetrics and Gynecology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China., Chen XL; Department of Obstetrics and Gynecology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China., Lin XL; Department of Obstetrics and Gynecology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China., Lee CL; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China.; Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong S.A.R., Chiu PCN; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China.; Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong S.A.R., Yeung WSB; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China.; Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong S.A.R., Yao YQ; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, P.R. China. yqyao@126.com.; Medical school of Chinese People's Liberation Army, Chinese People's Liberation Army General Hospital, Beijing, China. yqyao@126.com.; Department of Obstetrics and Gynecology, The First Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China. yqyao@126.com.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2023 Oct 18; Vol. 24 (1), pp. 618. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1186/s12864-023-09690-x
Abstrakt: 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.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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