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

Hiroko Nomaru (1) , Yang Liu (1) , Christopher de Bono (1) , Dario Righelli (2, 3) , Andrea Cirino (4) , Wei Wang (5) , Hansoo Song (1) , Silvia E Racedo (1) , Anelisa G Dantas (1, 6) , Lu Zhang (7) , Chen-Leng Cai (7) , Claudia Angelini (2) , Lionel Christiaen (5) , Robert G Kelly (8) , Antonio Baldini (4) , Deyou Zheng (1) , Bernice E Morrow (1)

1 Albert Einstein College of Medicine [New York]
2 Institute for Applied Computing, National Research Council, Naples, Italy
3 Unipd - Università degli Studi di Padova = University of Padua
4 University of Naples Federico II = Università degli studi di Napoli Federico II
5 Center for Developmental Genetics, Department of Biology, New York University, New York, NY, USA
6 Federal University of Sao Paulo, Sao Paulo, Brazil.
7 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
8 IBDM - Institut de Biologie du Développement de Marseille

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.

Mots clés: Cell lineage; Gene expression profiling; Mechanisms of disease; RNA sequencing

Domaines: Sciences du Vivant [q-bio]

Hiroko Nomaru, Yang Liu, Christopher de Bono, Dario Righelli, Andrea Cirino, et al.. Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm. Nature Communications, 2021, 12 (1), pp.6645. ⟨10.1038/s41467-021-26966-6⟩. ⟨hal-03572477⟩