The Regulatory Landscape of Lineage Differentiation in a Metazoan Embryo

Developmental Cell
Zhuo DuZhirong Bao

Abstract

Elucidating the mechanism of cell lineage differentiation is critical for our understanding of development and fate manipulation. Here we combined systematic perturbation and direct lineaging to map the regulatory landscape of lineage differentiation in early C. elegans embryogenesis. High-dimensional phenotypic analysis of 204 essential genes in 1,368 embryos revealed that cell lineage differentiation follows a canalized landscape with barriers shaped by lineage distance and genetic robustness. We assigned function to 201 genes in regulating lineage differentiation, including 175 switches of binary fate choices. We generated a multiscale model that connects gene networks and cells to the experimentally mapped landscape. Simulations showed that the landscape topology determines the propensity of differentiation and regulatory complexity. Furthermore, the model allowed us to identify the chromatin assembly complex CAF-1 as a context-specific repressor of Notch signaling. Our study presents a systematic survey of the regulatory landscape of lineage differentiation of a metazoan embryo.

References

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Citations

Jan 15, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Zhuxia ZhengHuayu Qi
Feb 27, 2016·Genesis : the Journal of Genetics and Development·Amanda L Zacharias, John Isaac Murray
May 3, 2016·Wiley Interdisciplinary Reviews. Developmental Biology·Oliver Hobert
Aug 9, 2016·Current Opinion in Genetics & Development·Joshua BloomekatzNeil C Chi
Nov 9, 2016·Nature Biotechnology·Stavroula SkylakiTimm Schroeder
Jan 26, 2018·Wiley Interdisciplinary Reviews. Developmental Biology·John Isaac Murray
Nov 26, 2019·BMC Bioinformatics·Hanxu HouJianye Hao
Jan 4, 2017·Developmental Cell·Wolfgang KeilEric D Siggia
Jul 12, 2017·Current Opinion in Genetics & Development·Sihem Cheloufi, Konrad Hochedlinger

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