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@ARTICLE{Riegel:210399,
author = {D. Riegel and E. Romero-Fernández and M. Simon$^*$ and A.
R. Adenugba and K. Singer and R. Mayr and F. Weber and M.
Kleemann and C. D. Imbusch$^*$ and M. Kreutz and B.
Brors$^*$ and I. Ugele and J. M. Werner and P. J. Siska and
C. Schmidl},
title = {{I}ntegrated single-cell profiling dissects
cell-state-specific enhancer landscapes of human
tumor-infiltrating {CD}8+ {T} cells.},
journal = {Molecular cell},
volume = {83},
number = {4},
issn = {1097-2765},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2023-00123},
pages = {622-636.e10.},
year = {2023},
note = {#EA:B330# / 83(4), pp. 622-636.e10. 2023},
abstract = {Despite extensive studies on the chromatin landscape of
exhausted T cells, the transcriptional wiring underlying the
heterogeneous functional and dysfunctional states of human
tumor-infiltrating lymphocytes (TILs) is incompletely
understood. Here, we identify gene-regulatory landscapes in
a wide breadth of functional and dysfunctional CD8+ TIL
states covering four cancer entities using single-cell
chromatin profiling. We map enhancer-promoter interactions
in human TILs by integrating single-cell chromatin
accessibility with single-cell RNA-seq data from
tumor-entity-matching samples and prioritize
cell-state-specific genes by super-enhancer analysis.
Besides revealing entity-specific chromatin remodeling in
exhausted TILs, our analyses identify a common chromatin
trajectory to TIL dysfunction and determine key enhancers,
transcriptional regulators, and deregulated genes involved
in this process. Finally, we validate enhancer regulation at
immunotherapeutically relevant loci by targeting non-coding
regulatory elements with potent CRISPR activators and
repressors. In summary, our study provides a framework for
understanding and manipulating cell-state-specific
gene-regulatory cues from human tumor-infiltrating
lymphocytes.},
keywords = {CRISPR activation (Other) / CRISPR interference (Other) / T
cell exhaustion (Other) / cancer immunology (Other) /
chromatin accessibility (Other) / enhancer (Other) / gene
regulation (Other) / single-cell ATAC-seq (Other) /
tumor-infiltrating T cells (Other)},
cin = {B330 / HD01},
ddc = {610},
cid = {I:(DE-He78)B330-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36657444},
doi = {10.1016/j.molcel.2022.12.029},
url = {https://inrepo02.dkfz.de/record/210399},
}