Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development

• During development, the lymphatic vasculature forms as a second, new vascular network derived from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is the first step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet downstream mechanisms remain to be elucidated. We present a single cell transcriptomic atlas of lymphangiogenesis in zebrafish revealing new markers and  hallmarks of LEC differentiation over four developmental stages. We further profile single  cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a VEC-LEC fate reversion during differentiation. Using maternal and zygotic  prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by  Prox1 during LEC specification. This work altogether reveals new transcriptional targets and regulatory regions of the genome downstream of Prox1 in LEC maintenance, as well as showing that Prox1 specifies LEC fate primarily by limiting blood vascular and  hematopoietic fate. This extensive single cell resource provides new mechanistic insights  into the enigmatic role of Prox1 and the control of LEC differentiation in development. 

Subject headings

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

Publication and Content Type

ref (subject category)

art (subject category)