Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development

Shangli Cheng; Yu Pei; Liqun He; Guangdun Peng; Björn Reinius; Patrick P L Tam; Naihe Jing; Qiaolin Deng

doi:10.1016/j.celrep.2019.02.031

Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development

Cell Rep. 2019 Mar 5;26(10):2593-2607.e3. doi: 10.1016/j.celrep.2019.02.031.

Authors

Shangli Cheng¹, Yu Pei², Liqun He³, Guangdun Peng⁴, Björn Reinius⁵, Patrick P L Tam⁶, Naihe Jing⁷, Qiaolin Deng⁸

Affiliations

¹ Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Solna, Sweden.
² Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Solna, Sweden; Center for Molecular Medicine, Karolinska University Hospital, 17176 Solna, Sweden.
³ Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, 300052 Tianjin, China.
⁴ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031 Shanghai, China; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510530 Guangzhou, China.
⁵ Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Solna, Sweden.
⁶ Embryology Unit, Children's Medical Research Institute, The University of Sydney and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
⁷ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031 Shanghai, China; School of Life Science and Technology, Shanghai Tech University, 201210 Shanghai, China.
⁸ Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Solna, Sweden; Center for Molecular Medicine, Karolinska University Hospital, 17176 Solna, Sweden; School of Life Sciences and Technology, Tongji University, 200092 Shanghai, China. Electronic address: qiaolin.deng@ki.se.

PMID: 30840884
DOI: 10.1016/j.celrep.2019.02.031

Abstract

Following implantation, the epiblast (EPI) cells transit from the naive to primed pluripotency, accompanied by dynamic changes in X chromosome activity in females. To investigate the molecular attributes of this process, we performed single-cell RNA-seq analysis of 1,724 cells of E5.25, E5.5, E6.25, and E6.5 mouse embryos. We identified three cellular states in the EPI cells that capture the transition along the pluripotency continuum and the acquisition of primitive streak propensity. The transition of three EPI states was driven by inductive signaling activity emanating from the visceral endoderm (VE). In the EPI of female embryos, X chromosome reactivation (XCR) was initiated prior to the completion of imprinted X chromosome inactivation (XCI), and the ensuing random XCI was highly asynchronous. Moreover, imprinted paternal XCI proceeded faster in the VE than the extraembryonic ectoderm. Our study has provided a detailed molecular roadmap of the emergent lineage commitment before gastrulation and characterized X chromosome dynamics during early mouse development.

Keywords: X chromosome inactivation dynamics; epiblast heterogeneity; pluripotency transition; pregastrula development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Lineage
Embryo Implantation / genetics*
Female
Mice
Sequence Analysis, RNA / methods*
X Chromosome / genetics*