Transcriptomics

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Gastrulation-stage gene expression in Nipbl+/- mouse embryos foreshadows the development of syndromic birth defects


ABSTRACT: In animal models, Nipbl-deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange Syndrome (CdLS), the most common cause of which is Nipbl-haploinsufficiency. Previous studies in Nipbl+/- mice identified aberrant gene expression and heart defects as early as cardiac crescent (CC) stage. Here, we performed single-cell RNA-sequencing on wildtype (WT) and Nipbl+/- mouse embryos at CC- and earlier (gastrulation) stages. Nipbl+/- embryos had fewer mesoderm cells than WT and altered proportions of mesodermal cell subpopulations. These findings were associated with an underexpression of genes implicated in driving specific mesodermal lineages. Nipbl+/- embryos also misexpressed developmentally-critical genes, including the transcription factor, Nanog, and genes governing left-right and anterior-posterior patterning. These events of cell misallocation and transcriptional dysregulation foreshadowed defects in tissue composition and patterning that arise later in Nipbl+/- mice, offering insights into early developmental contributions to birth defects in CdLS.

ORGANISM(S): Mus musculus

PROVIDER: GSE151589 | GEO | 2023/05/07

REPOSITORIES: GEO

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