TY - JOUR
T1 - Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
AU - Nomaru, Hiroko
AU - Liu, Yang
AU - De Bono, Christopher
AU - Righelli, Dario
AU - Cirino, Andrea
AU - Wang, Wei
AU - Song, Hansoo
AU - Racedo, Silvia
AU - Dantas, Anelisa G.
AU - Zhang, Lu
AU - Cai, Chen Leng
AU - Angelini, Claudia
AU - Christiaen, Lionel
AU - Kelly, Robert G.
AU - Baldini, Antonio
AU - Zheng, Deyou
AU - Morrow, Bernice E.
N1 - Funding Information:
We thank Genomics core, especially David Reynolds, Director of the Genomics Core, Shahina Maqbool, Director of the Epigenomics core as well as the Flow Cytometry and Gene modification facilities at Einstein. We appreciate all the help in data analysis and training by Masako Suzuki at Einstein. We thank Drs. Bin Zhou, Cedric Blanpain, and Peter Scambler for reading this manuscript and providing helpful suggestions. We also thank NYU Center for Genomics and Systems Biology Genomics Core; NYU Langone’s Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center, especially Peter Meyn. This work was supported by grants from the National Institutes of Health P01HD070454 (B.E.M. and D.Z.), R01HL153920 (B.E.M. and D.Z.), R01HD096770 (L.C.), and R01HL108643 (L.C.). The work was also supported by a grant from the Foundation Leducq (Transatlantic Network of Excellence 15CVD01; B.E.M., L.C., R.G.K., and A.B.) and the Agence Nationale de la Recherche Heartbox and Myohead projects (RGK). Dr. Nomaru was supported by an American Association Grant (19POST34380281).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-26966-6
DO - 10.1038/s41467-021-26966-6
M3 - Article
C2 - 34789765
AN - SCOPUS:85119249459
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6645
ER -