1. Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm.
- Author
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Nomaru H, Liu Y, De Bono C, Righelli D, Cirino A, Wang W, Song H, Racedo SE, Dantas AG, Zhang L, Cai CL, Angelini C, Christiaen L, Kelly RG, Baldini A, Zheng D, and Morrow BE
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Branchial Region embryology, Branchial Region metabolism, Cell Differentiation, Cell Lineage, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart embryology, Mesoderm embryology, Mesoderm metabolism, Mice, Mice, Transgenic, Muscle, Skeletal cytology, Muscle, Skeletal metabolism, Myocardium metabolism, Single-Cell Analysis, Stem Cells cytology, Stem Cells metabolism, T-Box Domain Proteins genetics, Branchial Region cytology, Mesoderm cytology, Myocardium cytology, T-Box Domain Proteins metabolism
- Abstract
The poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm within the pharyngeal apparatus. They are disrupted in patients with 22q11.2 deletion syndrome, due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we now identify a multilineage primed population within the cardiopharyngeal mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells. The multilineage primed cells are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of cardiopharyngeal mesoderm progenitors. Tbx1 regulates the maturation of multilineage primed progenitor cells to cardiopharyngeal mesoderm derivatives while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance of gene expression by direct and indirect regulation of enriched genes in multilineage primed progenitors and downstream pathways, partly through altering chromatin accessibility, the perturbation of which can lead to congenital defects in individuals with 22q11.2 deletion syndrome., (© 2021. The Author(s).)
- Published
- 2021
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