Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation

  1. Zhouchun Shang
  2. Dongsheng Chen
  3. Quanlei Wang
  4. Shengpeng Wang
  5. Qiuting Deng
  6. Liang Wu
  7. Chuanyu Liu
  8. Xiangning Ding
  9. Shiyou Wang
  10. Jixing Zhong
  11. Doudou Zhang
  12. Xiaodong Cai
  13. Shida Zhu
  14. Huanming Yang
  15. Longqi Liu
  16. J Lynn Fink
  17. Fang Chen
  18. Xiaoqing Liu
  19. Zhengliang Gao
  20. Xun Xu

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Abstract

Background

Investigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.

Results

In this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most toward commitment to the central nervous system lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active cis-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred in the embryoid body stage and that each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation that could reflect the identity of each subpopulation.

Conclusions

Our study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.

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  1. GigaScience

    Now published in GigaScience doi: 10.1093/gigascience/giy117

    Zhouchun Shang 1Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, China4Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteDongsheng Chen 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteQuanlei Wang 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, China4Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, Shenzhen, China5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteShengpeng Wang 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteQiuting Deng 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteLiang Wu 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, China5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China6Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteXiangning Ding 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteShiyou Wang 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteJixing Zhong 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteDoudou Zhang 7Department of Neurosurgery, Shenzhen Second People’s Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteXiaodong Cai 7Department of Neurosurgery, Shenzhen Second People’s Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteShida Zhu 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, China4Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteHuanming Yang 2BGI-Shenzhen, Shenzhen, China8James D. Watson Institute of Genome Sciences, Hangzhou, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteLongqi Liu 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteJ. Lynn Fink 2BGI-Shenzhen, Shenzhen, China9The University of Queensland, Diamantina Institute (UQDI), Brisbane, QLD, AustraliaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFang Chen 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, China10Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, DenmarkFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteXiaoqing Liu 1Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteZhengliang Gao 1Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFor correspondence: xuxun@genomics.cnXun Xu 2BGI-Shenzhen, Shenzhen, China3China National GeneBank, BGI-Shenzhen, Shenzhen, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFor correspondence: xuxun@genomics.cn

    A version of this preprint has been published in the Open Access journal GigaScience (see paper https://doi.org/10.1093/gigascience/giy117 ), where the paper and peer reviews are published openly under a CC-BY 4.0 license.

    These peer reviews were as follows:

    Reviewer 1: http://dx.doi.org/10.5524/REVIEW.101371 Reviewer 2: http://dx.doi.org/10.5524/REVIEW.101372

  2. Version published to 10.1093/gigascience/giy117
  3. Version published to 10.1101/384131v1 on bioRxiv