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Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo

Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yangyang Wang, Yanping Zhang, Gang Wu, View ORCID ProfileZhuo Du
doi: https://doi.org/10.1101/2020.06.30.178640
Xuehua Ma
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
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Zhiguang Zhao
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
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Long Xiao
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
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Weina Xu
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
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Yangyang Wang
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
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Yanping Zhang
3National Institute of Biological Science, Beijing 102206, China
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Gang Wu
3National Institute of Biological Science, Beijing 102206, China
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Zhuo Du
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
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  • ORCID record for Zhuo Du
  • For correspondence: zdu@genetics.ac.cn
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SUMMARY

A high-resolution protein atlas is essential for understanding the molecular basis of biological processes. Using protein-fusion reporters and imaging-based single-cell analyses, we present a protein expression atlas of C. elegans embryogenesis encompassing 266 transcription factors (TFs) in nearly all (90%) lineage-resolved cells. Single-cell analysis reveals a combinatorial code and cascade that elucidate the regulatory hierarchy between a large number of lineage-, tissue-, and time-specific TFs in spatiotemporal fate patterning. Guided by expression, we identify essential functions of CEH-43/DLX, a lineage-specific TF, and ELT-1/GATA3, a well-known skin fate specifier, in neuronal specification; and M03D4.4 as a pan-muscle TF in converging muscle differentiation in the body wall and pharynx. Finally, systems-level analysis of TF regulatory state uncovers lineage- and time-specific kinetics of fate progression and widespread detours of the trajectories of cell differentiation. Collectively, our work reveals a single-cell molecular atlas and general principles underlying the spatiotemporal patterning of a metazoan embryo.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 07, 2020.
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Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo
Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yangyang Wang, Yanping Zhang, Gang Wu, Zhuo Du
bioRxiv 2020.06.30.178640; doi: https://doi.org/10.1101/2020.06.30.178640
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Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo
Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yangyang Wang, Yanping Zhang, Gang Wu, Zhuo Du
bioRxiv 2020.06.30.178640; doi: https://doi.org/10.1101/2020.06.30.178640

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