GSE158941
Tbx1 regulates a cardiopharyngeal mesodermal niche in forming the heart and branchiomeric muscles [scRNA-Seq 1]
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. Overall design: Mesp1 gene expresses in early cardiac mesodermal cells. To capture mesodermal cell lineages,  sorted GFP positive cell from Mesp1-Cre/+;GFPflox/+ embryos at E8.0 to E10.5 embryos were used for scRNA-seq analysis.