Abstract
AbstractIn animal models,Nipbl-deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange Syndrome (CdLS), the most common cause of which isNipbl-haploinsufficiency. Previous studies inNipbl+/-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) andNipbl+/-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 inNipbl+/-mice, offering insights into early developmental contributions to birth defects in CdLS.TeaserGene expression changes during gastrulation ofNipbl-deficient mice shed light on early origins of structural birth defects.
Publisher
Cold Spring Harbor Laboratory
Reference123 articles.
1. Update on overall prevalence of major birth defects--Atlanta, Georgia, 1978-2005;C. Centers for Disease, Prevention;MMWR Morb Mortal Wkly Rep,2008
2. National population‐based estimates for major birth defects, 2010–2014
3. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments
4. Infant Mortality in the United States, 2020: Data From the Period Linked Birth/Infant Death File;Natl Vital Stat Rep,2022
5. Mutation Spectrum and Genotype-Phenotype Correlation in Cornelia de Lange Syndrome
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