Journal Article

DKFZ-2021-01164

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver.

Inverso, D. (First author)DKFZ* ; Shi, J.DKFZ* ; Lee, K. H.DKFZ* ; Jakab, M.DKFZ* ; Ben-Moshe, S. ; Kulkarni, S. R.DKFZ* ; Schneider, M.DKFZ* ; Wang, G.DKFZ* ; Komeili, M. ; Vélez, P. A.DKFZ* ; Riedel, M.DKFZ* ; Spegg, C.DKFZ* ; Ruppert, T. ; Schaeffer-Reiss, C. ; Helm, D.DKFZ* ; Singh, I.DKFZ* ; Boutros, M.DKFZ* ; Chintharlapalli, S. ; Heikenwalder, M.DKFZ* ; Itzkovitz, S. ; Augustin, H. (Last author)DKFZ*

2021
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.devcel.2021.05.001

Abstract: 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.

Keyword(s): Tie1 ; Tie2 ; Wnt ; angiocrine factors ; liver endothelial cell (L-EC) ; phosphoproteomics ; proteomics ; transcriptomics ; vascular zonation

Note: #EA:A190#LA:A190#/2021 Jun 7;56(11):1677-1693.e10

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Contributing Institute(s):

1. A190 Vaskuläre Onkologie und Metastatistierung (A190)
2. W120 Proteinanalyse (W120)
3. F180 Chronische Entzündung und Krebs (F180)
4. B110 Signalwege funktionelle Genomik (B110)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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