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Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE167493 | GEO | 2021/10/10

REPOSITORIES: GEO

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Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 2]

Project description:The heart and branchiomeric muscles are formed from the cardiopharyngeal mesoderm (CPM) during mammalian embryogenesis. The molecular mechanisms for lineage progression in the CPM in mammals remain elusive. Here, we have used single cell RNA-seq and lineage analysis and identified a cardiopharyngeal niche containing multilineage primed cells termed multilineage progenitors (MLPs), which is maintained throughout maturation of the pharyngeal apparatus. We found that MLP function is dependent on Tbx1, encoding a T-box transcription factor and the gene for 22q11.2 deletion syndrome. TBX1 positively regulates novel MLP enriched genes such as Aplnr and Nrg1, as well as known CPM genes related to both BrM and cardiac muscle cell development. Further, loss of Tbx1 results in ectopic expression of neuronal and other non-mesodermal specification genes such as Bdnf and Pax8, respectively, indicating that normal developmental regulation is disrupted. Integration of the multi-omic data generated a TBX1 gene regulatory network, including Isl1, Pitx2, Foxc2, Six1/2 and Tcf21, that regulates CPM lineage progression from MLPs. Our finding suggests that TBX1 is a one of the key regulators in MLP to maintain CPM property and promote differentiation toward both BrM and cardiac muscle cells.

2021-10-10 | GSE167491 | GEO

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 1]

2021-10-10 | GSE158941 | GEO

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 4]

2021-11-01 | GSE186934 | GEO

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 3]

2021-10-10 | GSE168768 | GEO

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles

Project description:Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles

| PRJNA704805 | ENA

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 4]

Project description:Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 4]

| PRJNA776834 | ENA

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 2]

Project description:Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 2]

| PRJNA704809 | ENA

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 1]

Project description:Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 1]

| PRJNA667066 | ENA

Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 3]

Project description:Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 3]

| PRJNA713848 | ENA

Tbx1 regulates proliferation and differentiation of multipotent heart progenitors.

Project description:TBX1 encodes a T-box transcription factor implicated in DiGeorge syndrome, which affects the development of many organs, including the heart. Loss of Tbx1 results into hypoplasia of heart regions derived from the second heart field, a population of cardiac progenitors cells (CPCs). Thus, we hypothesized that Tbx1 is an important player in the biology of CPCs.We asked whether Tbx1 is expressed in multipotent CPCs and, if so, what role it may play in them.We used clonal analysis of Tbx1-expressing cells and loss and gain of function models, in vivo and in vitro, to define the role of Tbx1 in CPCs. We found that Tbx1 is expressed in multipotent heart progenitors that, in clonal assays, can give rise to 3 heart lineages expressing endothelial, smooth muscle and cardiomyocyte markers. In multipotent cells, Tbx1 stimulates proliferation, explaining why Tbx1(-/-) embryos have reduced proliferation in the second heart field. In this population, Tbx1 is expressed while cells are undifferentiated and it disappears with the onset of muscle markers. Loss of Tbx1 results in premature differentiation, whereas gain results in reduced differentiation in vivo. We found that Tbx1 binds serum response factor, a master regulator of muscle differentiation, and negatively regulates its level.The Tbx1 protein marks CPCs, supports their proliferation, and inhibits their differentiation. We propose that Tbx1 is a key regulator of CPC homeostasis as it modulates positively their proliferation and negatively their differentiation.

| S-EPMC2796444 | biostudies-literature

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