Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta.

Yawei Liu, Xiaoying Fan, Rui Wang, Xiaoyin Lu, Yan-Li Dang, Huiying Wang, Hai-Yan Lin, Cheng Zhu, Hao Ge, James C Cross, Hongmei Wang
Author Information
  1. Yawei Liu: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  2. Xiaoying Fan: Biomedical Pioneering Innovation Center, College of Life Science, Peking University, 100871, Beijing, China.
  3. Rui Wang: Biomedical Pioneering Innovation Center, College of Life Science, Peking University, 100871, Beijing, China.
  4. Xiaoyin Lu: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  5. Yan-Li Dang: Department of Obstetrics and Gynecology, The 306th Hospital of PLA, 100101, Beijing, China.
  6. Huiying Wang: Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, 100038, Beijing, China.
  7. Hai-Yan Lin: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  8. Cheng Zhu: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  9. Hao Ge: Biomedical Pioneering Innovation Center, College of Life Science, Peking University, 100871, Beijing, China. ORCID
  10. James C Cross: Departments of Biochemistry and Molecular Biology, Comparative Biology and Experimental Medicine, Obstetrics and Gynecology, and Medical Genetics, University of Calgary, Calgary, AB, T2N 4N1, Canada. jcross@ucalgary.ca. ORCID
  11. Hongmei Wang: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China. wanghm@ioz.ac.cn.

Abstract

The placenta is crucial for a successful pregnancy and the health of both the fetus and the pregnant woman. However, how the human trophoblast lineage is regulated, including the categorization of the placental cell subtypes is poorly understood. Here we performed single-cell RNA sequencing (RNA-seq) on sorted placental cells from first- and second-trimester human placentas. New subtypes of cells of the known cytotrophoblast cells (CTBs), extravillous trophoblast cells (EVTs), Hofbauer cells, and mesenchymal stromal cells were identified and cell-type-specific gene signatures were defined. Functionally, this study revealed many previously unknown functions of the human placenta. Notably, 102 polypeptide hormone genes were found to be expressed by various subtypes of placental cells, which suggests a complex and significant role of these hormones in regulating fetal growth and adaptations of maternal physiology to pregnancy. These results document human placental trophoblast differentiation at single-cell resolution and thus advance our understanding of human placentation during the early stage of pregnancy.

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MeSH Term

Base Sequence
Cell Differentiation
Female
Gene Expression
Humans
Mesenchymal Stem Cells
Peptide Hormones
Placenta
Placentation
Pregnancy
Pregnancy Trimester, First
Pregnancy Trimester, Second
Sequence Analysis, RNA
Single-Cell Analysis
Trophoblasts

Chemicals

Peptide Hormones