Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development.
Nat Genet, 2022/07;54(7):1051-1061.
Fei L[1], Chen H[1, 2], Ma L[1], E W[1], Wang R[1], Fang X[1], Zhou Z[1], Sun H[1], Wang J[2], Jiang M[2], Wang X[1], Yu C[1], Mei Y[1], Jia D[1], Zhang T[2], Han X[3], Guo G[4, 5, 6, 7, 8]
Affiliations
PMID: 35817981DOI: 10.1038/s41588-022-01118-8
Impact factor: 41.307
Abstract
Waddington's epigenetic landscape is a metaphor frequently used to illustrate cell differentiation. Recent advances in single-cell genomics are altering our understanding of the Waddington landscape, yet the molecular mechanisms of cell-fate decisions remain poorly understood. We constructed a cell landscape of mouse lineage differentiation during development at the single-cell level and described both lineage-common and lineage-specific regulatory programs during cell-type maturation. We also found lineage-common regulatory programs that are broadly active during the development of invertebrates and vertebrates. In particular, we identified Xbp1 as an evolutionarily conserved regulator of cell-fate determinations across different species. We demonstrated that Xbp1 transcriptional regulation is important for the stabilization of the gene-regulatory networks for a wide range of mouse cell types. Our results offer genetic and molecular insights into cellular gene-regulatory programs and will serve as a basis for further advancing the understanding of cell-fate decisions.
MeSH terms
Animals; Cell Differentiation; Cell Lineage; Epigenesis, Genetic; Epigenomics; Gene Regulatory Networks; Mice; Models, Genetic
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