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

52 Pages Posted: 16 Aug 2018 Last revised: 11 Jun 2019 Sneak Peek Status: Published

See all articles by Shangli Cheng

Shangli Cheng

Karolinska Institutet - Department of Physiology and Pharmacology

Yu Pei

Karolinska Institutet - Department of Physiology and Pharmacology

Liqun He

Tianjin Medical University - Department of Neurosurgery

Guangdun Peng

Chinese Academy of Sciences (CAS), Shanghai Institutes for Biological Sciences, Institute of Biochemistry and Cell Biology, State Key Laboratory of Cell Biology

Björn Reinius

Karolinska Institutet - Department of Medical Biochemistry and Biophysics

Patrick P. L. Tam

Children's Medical Research Institute (CMRI) - Embryology Unit

Naihe Jing

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

Qiaolin Deng

Karolinska Institutet - Department of Physiology and Pharmacology

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Abstract

Following implantation, the epiblast (EPI) cells transit from the naïve to the primed pluripotency state in preparation for gastrulation, a momentous developmental milestone of the formation of the three primary germ layers. To investigate the molecular attributes of this critical developmental process of lineage specification and the dynamic changes in X-chromosome activity, we performed Smart-seq2 single-cell RNA-seq analysis of 1724 mouse E5.25 to E6.5 embryonic cells. We identified three distinct cellular states in the EPI cells that mirrors the transition of postimplantation EPI along the continuum of naïve to primed pluripotency and the acquisition of primitive streak propensity over time. The transition of the EPI cellular state was accompanied by enhanced interaction with the visceral endoderm mediated by inductive signalling activity. By tracing X-chromosome activity at the allelic resolution, we discovered that X-chromosome reactivation (XCR) was initiated prior to the complete silencing of imprinted X-chromosome in the EPI, and followed by asynchronous random X-chromosome inactivation (XCI). Moreover, imprinted X-chromosome inactivation proceeded with a faster kinetics in the visceral endoderm compared to the extraembryonic ectoderm. Our study has outlined in detail a molecular roadmap of the emergent process of lineage specification and X-chromosome reprogramming during mouse pregastrulation development.

Suggested Citation

Cheng, Shangli and Pei, Yu and He, Liqun and Peng, Guangdun and Reinius, Björn and Tam, Patrick P. L. and Jing, Naihe and Deng, Qiaolin, Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X-Chromosome Dynamics During Early Postimplantation Mouse Development. Available at SSRN: https://ssrn.com/abstract=3231846 or http://dx.doi.org/10.2139/ssrn.3231846
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Shangli Cheng

Karolinska Institutet - Department of Physiology and Pharmacology

Solnavägen 9
Stockholm, SE-171 77
Sweden

Yu Pei

Karolinska Institutet - Department of Physiology and Pharmacology

Solnavägen 9
Stockholm, SE-171 77
Sweden

Liqun He

Tianjin Medical University - Department of Neurosurgery

Tianjin Shi
China

Guangdun Peng

Chinese Academy of Sciences (CAS), Shanghai Institutes for Biological Sciences, Institute of Biochemistry and Cell Biology, State Key Laboratory of Cell Biology

Shanghai
China

Björn Reinius

Karolinska Institutet - Department of Medical Biochemistry and Biophysics

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Patrick P. L. Tam

Children's Medical Research Institute (CMRI) - Embryology Unit

Westmead, NSW 2145
Australia

Naihe Jing

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

320 Yue Yang Road
Shanghai, 200031
China

Qiaolin Deng (Contact Author)

Karolinska Institutet - Department of Physiology and Pharmacology ( email )

Solnavägen 9
Stockholm, SE-171 77
Sweden

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