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  3. Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy

Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy

  • Nat Genet. 2024 Jan 24. doi: 10.1038/s41588-023-01647-w.
Meijiao Wang # 1 2 3,  Yawei Liu # 1 2 4 5 6,  Run Sun # 1 2 7,  Fenting Liu # 8 9 10 11,  Jiaqian Li 12,  Long Yan 1 2 7,  Jixiang Zhang 3 7,  Xinwei Xie 12,  Dongxu Li 3,  Yiming Wang 1 2 7,  Shiwen Li 1 2 7,  Xili Zhu 1 2 7,  Rong Li 13 14 15 16,  Falong Lu 17 18,  Zhenyu Xiao 19 20,  Hongmei Wang 21 22 23
Affiliations

Affiliations

  • 1 The Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
  • 3 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • 4 Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.
  • 5 Medical Center of Soochow University, Suzhou, China.
  • 6 Suzhou Dushu Lake Hospital, Suzhou, China.
  • 7 University of Chinese Academy of Sciences, Beijing, China.
  • 8 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • 9 National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • 10 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China.
  • 11 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, China.
  • 12 School of Life Science, Beijing Institute of Technology, Beijing, China.
  • 13 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China. roseli001@sina.com.
  • 14 National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China. roseli001@sina.com.
  • 15 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China. roseli001@sina.com.
  • 16 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, China. roseli001@sina.com.
  • 17 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. fllu@genetics.ac.cn.
  • 18 University of Chinese Academy of Sciences, Beijing, China. fllu@genetics.ac.cn.
  • 19 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. xiaozy@bit.edu.cn.
  • 20 School of Life Science, Beijing Institute of Technology, Beijing, China. xiaozy@bit.edu.cn.
  • 21 The Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. wanghm@ioz.ac.cn.
  • 22 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. wanghm@ioz.ac.cn.
  • 23 University of Chinese Academy of Sciences, Beijing, China. wanghm@ioz.ac.cn.
  • # Contributed equally.
PMID: 38267607 DOI: 10.1038/s41588-023-01647-w
Abstract

The human placenta has a vital role in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA Sequencing and single-nucleus ATAC Sequencing analyses of human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their correspondence with human trophoblast stem cell (hTSC)-derived STB. Furthermore, we identified transcription factors associated with diverse STB nuclear lineages through their gene regulatory networks and experimentally confirmed their function in hTSC and trophoblast organoid-derived STBs. Together, our data provide insights into the heterogeneity of human STB and represent a valuable resource for interpreting associated pregnancy complications.

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