Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm.

Autor: Nomaru H; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Liu Y; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., De Bono C; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Righelli D; Institute for Applied Computing, National Research Council, Naples, Italy.; Department of Statistical Sciences, University of Padova, Padova, Italy., Cirino A; Department of Molecular Medicine and Medical Biotechnology, University Federico II School of Medicine, Naples, Italy.; Institute of Genetics and Biophysics, National Research Council, Naples, Italy., Wang W; Center for Developmental Genetics, Department of Biology, New York University, New York, NY, USA., Song H; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Racedo SE; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Dantas AG; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.; Federal University of Sao Paulo, Sao Paulo, Brazil., Zhang L; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA., Cai CL; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA., Angelini C; Institute for Applied Computing, National Research Council, Naples, Italy., Christiaen L; Center for Developmental Genetics, Department of Biology, New York University, New York, NY, USA., Kelly RG; Aix-Marseille University, CNRS UMR 7288, IBDM, Marseille, France., Baldini A; Department of Molecular Medicine and Medical Biotechnology, University Federico II School of Medicine, Naples, Italy.; Institute of Genetics and Biophysics, National Research Council, Naples, Italy., Zheng D; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Morrow BE; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA. bernice.morrow@einsteinmed.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 17; Vol. 12 (1), pp. 6645. Date of Electronic Publication: 2021 Nov 17.
DOI: 10.1038/s41467-021-26966-6
Abstrakt: 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).)
Databáze: MEDLINE
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