PLX120323

GSE79306: Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Purpose: Exploring mechanisms defining the unique nature of vascular development and differentiation in the brain .; Methods: High-resolution gene expression profiles of embryonic endothelial cells (EC) using translating ribosome affinity purification (TRAP) and single cell RNA-sequencing. RNA-sequenzing of transcription factor infected HUVEC.; Results: Comparisons of different organ-, temporal- or Ctnnb1 knock out-specific vascular translatomes revealed extensive molecular changes during the unique development of the brain endothelium. We identified brain endothelial-specific transcription factors Foxf2, Foxl2, Foxq1, Lef1, Ppard, Zfp551 and Zic3 that are associated with the temporal maturation of the blood-brain barrier and act downstream of the Wnt/Ctnnb1 signaling pathway. Profiling individual EC revealed a remarkable heterogeneity. Nevertheless, high levels of Foxf2, Foxq1, Ppard and Zic3 were correlated with elevated expression of differentiation markers. This could be recapitulated in vitro, where expression of Foxf2 and Zic3 in HUVEC led to an induction of blood-brain barrier differentiation markers.; Conclusions: Our study provides further insights into the temporal and cellular complexity of the developing embryonic brain endothelium. Our data raises many questions and provides a basis for further studies aiming to unravel cellular and molecular mechanisms that underlie vascular development and differentiation in the CNS. We anticipate that additional investigation of the identified transcription factors is likely to be a fruitful approach in understanding and manipulating the development of BBB and to engineer more advanced blood brain barrier in vitro models. SOURCE: Mike Hupe (Mike.Hupe@uni-wuerzburg.de) - University of Würzburg