Single-cell RNA sequencing reveals regulatory mechanism for trophoblast cell-fate divergence in human peri-implantation conceptuses

PLoS Biol. 2019 Oct 9;17(10):e3000187. doi: 10.1371/journal.pbio.3000187. eCollection 2019 Oct.


Multipotent trophoblasts undergo dynamic morphological movement and cellular differentiation after conceptus implantation to generate placenta. However, the mechanism controlling trophoblast development and differentiation during peri-implantation development in human remains elusive. In this study, we modeled human conceptus peri-implantation development from blastocyst to early postimplantation stages by using an in vitro coculture system and profiled the transcriptome of 476 individual trophoblast cells from these conceptuses. We revealed the genetic networks regulating peri-implantation trophoblast development. While determining when trophoblast differentiation happens, our bioinformatic analysis identified T-box transcription factor 3 (TBX3) as a key regulator for the differentiation of cytotrophoblast (CT) into syncytiotrophoblast (ST). The function of TBX3 in trophoblast differentiation is then validated by a loss-of-function experiment. In conclusion, our results provided a valuable resource to study the regulation of trophoblasts development and differentiation during human peri-implantation development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation
  • Computational Biology / methods
  • Embryo Implantation / genetics
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Models, Biological*
  • Single-Cell Analysis
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • Transcriptome*
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*
  • Zygote


  • T-Box Domain Proteins
  • TBX3 protein, human

Grant support

The research was funded by grants from the National Natural Science Foundation of China (81430026 (Key Program), and 81771651, ZX; 81873832, YZ)(; National Key R&D Program of China (2017YFC1001301, ZX and YZ; 2016YFC1000208, ZX), (; the Basic Research Projects of Shanghai Science and Technology Commission (16JC1404700, ZX)( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.