2. Academic Validation
  3. Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells

Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells

  • Sci Adv. 2021 Aug 11;7(33):eabf4416. doi: 10.1126/sciadv.abf4416.
Yanxing Wei 1 2 3,  Tianyu Wang 4 5,  Lishi Ma 1 2,  Yanqi Zhang 4,  Yuan Zhao 4,  Kathryn Lye 3 6,  Lu Xiao 1 2,  Chunlin Chen 2,  Zhijian Wang 2,  Yanlin Ma 7,  Xiaohua Zhou 1 8,  Fei Sun 2,  Weili Li 2,  Caroline Dunk 3,  Siliang Li 3 9,  Andras Nagy 3 10 11 12,  Yanhong Yu 1 2,  Guangjin Pan 13,  Stephen J Lye 14 10 15 16,  Yongli Shan 17 2 4
Affiliations

Affiliations

  • 1 Placenta Research Group, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 2 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 3 Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5T3H7, Canada.
  • 4 CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 5 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 6 Institute of Medical Science, University of Toronto, Toronto M5G1L4, Canada.
  • 7 Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education, Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 570102, China.
  • 8 Department of Obstetrics and Gynecology, The Second People's Hospital of Shenzhen, The First Hospital Affiliated to Shenzhen University, Shenzhen 518029, China.
  • 9 China National Gene Bank-Shenzhen, Shenzhen 518083, China.
  • 10 Department of Obstetrics & Gynecology, University of Toronto, Toronto M5G1L4, Canada.
  • 11 Institute of Medical Science, University of Toronto, Toronto M5S 1A8, Canada.
  • 12 Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
  • 13 CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. [email protected] [email protected] [email protected].
  • 14 Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5T3H7, Canada. [email protected] [email protected] [email protected].
  • 15 Department of Physiology, University of Toronto, Toronto M5G1L4, Canada.
  • 16 Department of Medicine, University of Toronto, Toronto M5G1L4, Canada.
  • 17 Placenta Research Group, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. [email protected] [email protected] [email protected].
PMID: 34380613 DOI: 10.1126/sciadv.abf4416
Abstract

Human trophoblast stem cells (hTSCs) provide a valuable model to study placental development and function. While primary hTSCs have been derived from embryos/early placenta, and transdifferentiated hTSCs from naïve human pluripotent stem cells (hPSCs), the generation of hTSCs from primed PSCs is problematic. We report the successful generation of TSCs from primed hPSCs and show that BMP4 substantially enhances this process. TSCs derived from primed hPSCs are similar to blastocyst-derived hTSCs in terms of morphology, proliferation, differentiation potential, and gene expression. We define the chromatin accessibility dynamics and histone modifications (H3K4me3/H3K27me3) that specify hPSC-derived TSCs. Consistent with low density of H3K27me3 in primed hPSC-derived hTSCs, we show that knockout of H3K27 methyltransferases (EZH1/2) increases the efficiency of hTSC derivation from primed hPSCs. Efficient derivation of hTSCs from primed hPSCs provides a simple and powerful model to understand human trophoblast development, including the pathogenesis of trophoblast-related disorders, by generating disease-specific hTSCs.

Figures
Products