The regulatory landscape of lineage differentiation in a metazoan embryo Journal Article

   


Authors: Du, Z.; Santella, A.; He, F.; Shah, P. K.; Kamikawa, Y.; Bao, Z.
Article Title: The regulatory landscape of lineage differentiation in a metazoan embryo
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. © 2015 Elsevier Inc.
Keywords: nonhuman; dna replication; phenotype; embryo; cell fate; embryo development; gene function; daughter cell; cell differentiation; cell lineage; stem cell; gene silencing; regulator gene; cell manipulation; time lapse imaging; essential gene; priority journal; article
Journal Title: Developmental Cell
Volume: 34
Issue: 5
ISSN: 1534-5807
Publisher: Cell Press  
Date Published: 2015-09-14
Start Page: 592
End Page: 607
Language: English
DOI: 10.1016/j.devcel.2015.07.014
PROVIDER: scopus
PMCID: PMC4573902
PUBMED: 26321128
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84942363569&partnerID=40&md5=4e1d0b25f77a134e0059fe3c0e5a96b0
Notes: Export Date: 2 November 2015 -- Source: Scopus
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MSK Authors
  1. Anthony Santella
    40 Santella
  2. Zhuo Du
    9 Du
  3. Zhirong Bao
    56 Bao
  4. Fei He
    3 He
  5. Pavak Kirit Shah
    7 Shah
  6. Yuko Kamikawa
    1 Kamikawa
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