Characterization of organ-level specification of murine vascular endothelial cells from embryonic-stage to post-puberty adulthood.

ABSTRACT: Vascular endothelial cells (ECs) establish via paracrine signaling tissue-specific niches that promote organ revascularization and regeneration. Given these executive functions, transplantation of ECs into the vasculature has been used to stimulate organ repair. However, challenges in faithfully deriving tissue-specific endothelium within in vitro culture conditions limit large-scale expansion potential, long-term functional stability, and the cell homing and engraftment potential towards the target organ. Identification of the transcriptional regulators that modulate the specification of generic or unspecified endothelial cell populations into tissue-specific vascular ECs may provide novel factors to be incorporated into standard stem-cell differentiation protocols. Such controlled expression of the appropriate angiocrine factors—in combination with the niche microenvironment—could support the necessary crosstalk and cell-to-cell membrane interactions necessary for positioning and anastomosis when transplanted. Previously, investigation of the transcriptome profiles of ECs originating from diverse vascular beds has helped identify potential transcriptional regulators and gene markers of EC tissue specification. We aim to expand on these studies by elaborating on the progression of EC tissue specification as it occurs from embryonic development to adulthood. A better understanding of how ECs acquire their tissue specificity and deconvolution of the transient expression patterns of key molecular regulators could provide crucial information on the establishment of EC tissue-specific function which can then be recapitulated in vitro. Our long-term goal is to generate transcriptionally stable and functional tissue-specific ECs from stem-cell derived EC banks suitable for transplantation for the purpose of promoting non-fibrotic tissue regeneration after organ injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE129005 | GEO | 2019/09/20

REPOSITORIES: GEO