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

Hiroko Nomaru, Yang Liu, Christopher De Bono, Dario Righelli, Andrea Cirino, Wei Wang, Hansoo Song, Silvia E. Racedo, Anelisa G. Dantas, Lu Zhang, Chen-Leng Cai, Claudia Angelini, Lionel Christiaen, Robert G. Kelly, Antonio Baldini, Deyou Zheng and Bernice E. Morrow ()
Additional contact information
Hiroko Nomaru: Department of Genetics, Albert Einstein College of Medicine
Yang Liu: Department of Genetics, Albert Einstein College of Medicine
Christopher De Bono: Department of Genetics, Albert Einstein College of Medicine
Dario Righelli: Institute for Applied Computing, National Research Council
Andrea Cirino: University Federico II School of Medicine
Wei Wang: New York University
Hansoo Song: Department of Genetics, Albert Einstein College of Medicine
Silvia E. Racedo: Department of Genetics, Albert Einstein College of Medicine
Anelisa G. Dantas: Department of Genetics, Albert Einstein College of Medicine
Lu Zhang: Indiana University School of Medicine
Chen-Leng Cai: Indiana University School of Medicine
Claudia Angelini: Institute for Applied Computing, National Research Council
Lionel Christiaen: New York University
Robert G. Kelly: Aix-Marseille University, CNRS UMR 7288, IBDM
Antonio Baldini: University Federico II School of Medicine
Deyou Zheng: Department of Genetics, Albert Einstein College of Medicine
Bernice E. Morrow: Department of Genetics, Albert Einstein College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26966-6

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