An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
27
05
2021
accepted:
25
10
2021
revised:
13
10
2021
pubmed:
11
11
2021
medline:
12
4
2022
entrez:
10
11
2021
Statut:
ppublish
Résumé
Cancer cells' ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.
Identifiants
pubmed: 34754079
doi: 10.1038/s41418-021-00895-9
pii: 10.1038/s41418-021-00895-9
pmc: PMC8990071
doi:
Substances chimiques
Mitochondrial Proteins
0
X-Linked Inhibitor of Apoptosis Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
806-817Subventions
Organisme : NCI NIH HHS
ID : R01 CA208179
Pays : United States
Organisme : Wellcome Trust
ID : 110371/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S021205/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 24387
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T002824/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400302
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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