A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver.
Endothelial Cells
/ metabolism
Endothelium
/ growth & development
Flow Cytometry
Gene Expression Regulation, Developmental
/ genetics
Hepatocytes
/ metabolism
Humans
Liver
/ growth & development
Liver Regeneration
/ genetics
Phosphoproteins
/ genetics
Phosphorylation
/ genetics
Proteomics
/ methods
RNA-Seq
Regeneration
/ genetics
Single-Cell Analysis
Transcriptome
/ genetics
Wnt Signaling Pathway
/ genetics
Tie1
Tie2
Wnt
angiocrine factors
liver endothelial cell (L-EC)
phosphoproteomics
proteomics
transcriptomics
vascular zonation
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
10
11
2020
revised:
18
02
2021
accepted:
30
04
2021
pubmed:
27
5
2021
medline:
21
10
2021
entrez:
26
5
2021
Statut:
ppublish
Résumé
Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of the spatial architecture of tissue structure and function. Advancing the "transcript-centric" view of scRNA-seq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyze post-translational modifications. Here, by combining spatial cell sorting with transcriptomics and quantitative proteomics/phosphoproteomics, we established the spatially resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signaling mechanisms. Phosphorylation of receptor tyrosine kinases was detected preferentially in the central vein area, resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation identified Tie receptor signaling as a selective and specific regulator of vascular Wnt activity orchestrating angiocrine signaling, thereby controlling hepatocyte function during liver regeneration. Taken together, the study has yielded fundamental insight into the spatial organization of liver endothelial cell signaling. Spatial sorting may be employed as a universally adaptable strategy for multiomic analyses of scRNA-seq-defined cellular (sub)-populations.
Identifiants
pubmed: 34038707
pii: S1534-5807(21)00401-9
doi: 10.1016/j.devcel.2021.05.001
pmc: PMC8191494
pii:
doi:
Substances chimiques
Phosphoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1677-1693.e10Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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