RRC ID 60826
Author Grosswendt S, Kretzmer H, Smith ZD, Kumar AS, Hetzel S, Wittler L, Klages S, Timmermann B, Mukherji S, Meissner A.
Title Epigenetic regulator function through mouse gastrulation.
Journal Nature
Abstract During ontogeny, proliferating cells become restricted in their fate through the combined action of cell-type-specific transcription factors and ubiquitous epigenetic machinery, which recognizes universally available histone residues or nucleotides in a context-dependent manner1,2. The molecular functions of these regulators are generally well understood, but assigning direct developmental roles to them is hampered by complex mutant phenotypes that often emerge after gastrulation3,4. Single-cell RNA sequencing and analytical approaches have explored this highly conserved, dynamic period across numerous model organisms5-8, including mouse9-18. Here we advance these strategies using a combined zygotic perturbation and single-cell RNA-sequencing platform in which many mutant mouse embryos can be assayed simultaneously, recovering robust  morphological and transcriptional information across a panel of ten essential regulators. Deeper analysis of central Polycomb repressive complex (PRC) 1 and 2 components indicates substantial cooperativity, but distinguishes a dominant role for PRC2 in restricting the germline. Moreover, PRC mutant phenotypes emerge after gross epigenetic and transcriptional changes within the initial conceptus prior to gastrulation. Our experimental framework may eventually lead to a fully quantitative view of how cellular diversity emerges using an identical genetic template and from a single totipotent cell.
Volume 584(7819)
Pages 102-108
Published 2020-8-1
DOI 10.1038/s41586-020-2552-x
PII 10.1038/s41586-020-2552-x
PMID 32728215
PMC PMC7415732
MeSH Animals Cell Lineage Epigenesis, Genetic* Female Gastrula / cytology Gastrula / embryology* Gastrula / metabolism* Gastrulation / genetics* Gene Expression Regulation, Developmental Male Mice Mutation Polycomb Repressive Complex 1 / metabolism Polycomb Repressive Complex 2 / metabolism Single-Cell Analysis Transcription, Genetic
IF 43.07
Times Cited 0
Mice RBRC05384