Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing

Background: The placenta is an important organ for fetal and maternal health during pregnancy and impacts offspring health late in life. Defects in placental vasculature and trophoblast have been identified in several pregnancy complications. Thus, the detailed molecular profile and heterogeneity of...

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Main Authors: Han Li, Hao Peng, Wei Hong, Yingying Wei, Haojun Tian, Xiaojie Huang, Linyan Jia, Jing Zheng, Tao Duan, Qizhi He, Kai Wang
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/1/87
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author Han Li
Hao Peng
Wei Hong
Yingying Wei
Haojun Tian
Xiaojie Huang
Linyan Jia
Jing Zheng
Tao Duan
Qizhi He
Kai Wang
author_facet Han Li
Hao Peng
Wei Hong
Yingying Wei
Haojun Tian
Xiaojie Huang
Linyan Jia
Jing Zheng
Tao Duan
Qizhi He
Kai Wang
author_sort Han Li
collection DOAJ
description Background: The placenta is an important organ for fetal and maternal health during pregnancy and impacts offspring health late in life. Defects in placental vasculature and trophoblast have been identified in several pregnancy complications. Thus, the detailed molecular profile and heterogeneity of endothelial cells and trophoblasts in placentas will aid us in better understanding placental behaviors and improving pregnancy outcomes. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to profile the transcriptomics of human placental villous tissues from eleven patients with normal pregnancies in the first and second trimesters (6–16 weeks of gestation). Results: The transcriptomic landscape of 52,179 single cells was obtained, and the cells were classified as trophoblasts, fibroblasts, endothelial cells, erythroid cells, Hofbauer cells, and macrophages. Our analysis further revealed the three subtypes of placental endothelial cells, with distinct metabolic signatures and transcription factor regulatory networks. We also determined the transcriptomic features of the trophoblast subpopulations and characterized two distinct populations of progenitor cells in cytotrophoblasts, which were capable of differentiating to extravillous trophoblasts and syncytiotrophoblasts, respectively. Conclusions: Our study provided a high-resolution molecular profile of the human placenta between 6 and 16 weeks of gestation. Our data revealed the placental cell complexity and demonstrated the transcriptional networks and signaling involved in placental endothelial and trophoblast differentiation during early pregnancy, which will be a resource for future studies of the human placental development.
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spelling doaj.art-2f1b65f3bc7542f7bc28902890db3f0f2023-11-16T15:05:56ZengMDPI AGCells2073-44092022-12-011218710.3390/cells12010087Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA SequencingHan Li0Hao Peng1Wei Hong2Yingying Wei3Haojun Tian4Xiaojie Huang5Linyan Jia6Jing Zheng7Tao Duan8Qizhi He9Kai Wang10Clinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaDepartment of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53715, USADepartment of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaDepartment of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaBackground: The placenta is an important organ for fetal and maternal health during pregnancy and impacts offspring health late in life. Defects in placental vasculature and trophoblast have been identified in several pregnancy complications. Thus, the detailed molecular profile and heterogeneity of endothelial cells and trophoblasts in placentas will aid us in better understanding placental behaviors and improving pregnancy outcomes. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to profile the transcriptomics of human placental villous tissues from eleven patients with normal pregnancies in the first and second trimesters (6–16 weeks of gestation). Results: The transcriptomic landscape of 52,179 single cells was obtained, and the cells were classified as trophoblasts, fibroblasts, endothelial cells, erythroid cells, Hofbauer cells, and macrophages. Our analysis further revealed the three subtypes of placental endothelial cells, with distinct metabolic signatures and transcription factor regulatory networks. We also determined the transcriptomic features of the trophoblast subpopulations and characterized two distinct populations of progenitor cells in cytotrophoblasts, which were capable of differentiating to extravillous trophoblasts and syncytiotrophoblasts, respectively. Conclusions: Our study provided a high-resolution molecular profile of the human placenta between 6 and 16 weeks of gestation. Our data revealed the placental cell complexity and demonstrated the transcriptional networks and signaling involved in placental endothelial and trophoblast differentiation during early pregnancy, which will be a resource for future studies of the human placental development.https://www.mdpi.com/2073-4409/12/1/87human placentascRNA-seqtrophoblastendothelial cellpregnancy
spellingShingle Han Li
Hao Peng
Wei Hong
Yingying Wei
Haojun Tian
Xiaojie Huang
Linyan Jia
Jing Zheng
Tao Duan
Qizhi He
Kai Wang
Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
Cells
human placenta
scRNA-seq
trophoblast
endothelial cell
pregnancy
title Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
title_full Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
title_fullStr Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
title_full_unstemmed Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
title_short Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing
title_sort human placental endothelial cell and trophoblast heterogeneity and differentiation revealed by single cell rna sequencing
topic human placenta
scRNA-seq
trophoblast
endothelial cell
pregnancy
url https://www.mdpi.com/2073-4409/12/1/87
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