Qi Chen

Guangzhou Institutes of Biomedicine and Health, CAS, China

Endothelial cells are a vital component of the vertebrate circulatory system, yet the  processes  and  mechanisms  by  which  they  acquire organ-specific transcriptional heterogeneity remain unclear. Therefore, we constructed a time-series endothelial cell resource library covering the  entire  embryonic  development  of  mice.  Through  time-series multi-organ comparisons, we  revealed the timing of organ-specific endothelial  cell  emergence,  lineage  trajectories,  critical  periods  of

differentiation, as well as organ-specific genes and pathways. Using this resource library, we discovered   that    most    endothelial   cells    already    exhibit   distinguishable    organ-specific characteristics  by  mid-gestation.  Human  and  mouse  lung  endothelial  cells  undergo  an evolutionarily   conserved   transcriptional   shift.    Endothelial   cell-specific   knockout   of   the lung-enriched  transcription  factor  Casz1  resulted  in  impaired  pulmonary  vascular  growth, disrupted   organ-specific   differentiation    of   lung    endothelial   cells,    and   defective    lung epithelial-endothelial cell interactions.