Single-cell transcriptomics of mouse wildtype and Hoxa2-/- pharyngeal arches 1 and 2 at E10.5.

ABSTRACT: The Hox genes play a key role in specifying the axial identity of neural crest cells (NCCs) migrating into the pharyngeal arches of the developing mouse embryo. In the absence of Hoxa2, NCC derivatives of the second pharyngeal arch (PA2) duplicate those formed by NCCs of the first arch (PA1). In this study, we use bulk and single-cell RNAseq to establish the molecular mechanisms driving this phenotypic reversion to a ground state. Comparing the transcriptomes of PA1 and PA2 in wildtype and Hoxa2-/- embryos during NCC migration and differentiation, we find that Hoxa2-/- PA2 does not revert to a molecular ‘ground state’ corresponding to the NCC derivatives. This separation of phenotypic and molecular states has significant implications for our understanding of NCC biology. We also identify putative targets through which HOXA2 likely acts to impart PA2 identity. The heterogenous expression of these targets within the PAs and their responses to the absence of HOXA2 suggest that subsets of NCCs may respond to HOXA2 activity in distinct manners related to their ultimate fate. To understand the heterogeneity of neural crest cells (NCCs) and other tissues of pharyngeal arches (PAs) 1 and 2 in the mouse embryo at E10.5, during NCC differentiation, we collected PA1 and PA2 from wildtype embryos and Hoxa2-/- embryos. We used the 10x Chromium single-cell sequencing system to compare the transcriptional profiles between PA1 and PA2 as well as wildtype and Hoxa2-/- PAs.

ORGANISM(S): Mus musculus

PROVIDER: GSE164108 | GEO | 2021/02/09

REPOSITORIES: GEO