Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development.
Notch1
Prox1
Vegfc single-cell sequencing
lymphangiogenesis
lymphatics
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
revised:
24
01
2023
received:
13
09
2022
accepted:
03
02
2023
pmc-release:
13
03
2024
medline:
2
6
2023
pubmed:
14
3
2023
entrez:
13
3
2023
Statut:
ppublish
Résumé
During development, the lymphatic vasculature forms as a second network derived chiefly from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is a key step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet the downstream mechanisms remain to be elucidated. We here 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 LEC-VEC fate shift. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new downstream targets and regulatory regions of the genome controlled by Prox1 and presents evidence that Prox1 specifies LEC fate primarily by limiting blood vascular and haematopoietic fate. This extensive single-cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development.
Identifiants
pubmed: 36912146
doi: 10.15252/embj.2022112590
pmc: PMC10233382
doi:
Substances chimiques
Homeodomain Proteins
0
Tumor Suppressor Proteins
0
Transcription Factors
0
Banques de données
GEO
['GSE188342']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e112590Informations de copyright
© 2023 The Authors.
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