Evidence map›Paper›PMID 38426634›Full record

ArticleClinical and translational medicine2024

Analysis of single nuclear chromatin accessibility reveals unique myeloid populations in human pancreatic ductal adenocarcinoma.

Hillary G Pratt, Li Ma, Sebastian A Dziadowicz, Sascha Ott, Thomas Whalley, Barbara Szomolay, Timothy D Eubank, Gangqing Hu, Brian A Boone

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Hillary G PrattCancer Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
Li MaDepartment of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
Sebastian A DziadowiczDepartment of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
Sascha OttWarwick Medical School, University of Warwick, Coventry, UK.
Thomas WhalleySchool of Biosciences, Cardiff University, Cardiff, UK.
Barbara SzomolayDivision of Infection and Immunity & Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
Timothy D EubankCancer Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
Gangqing HuWVU Cancer Institute, West Virginia University, Morgantown, West Virginia, USA.
Brian A BooneCancer Cell Biology, West Virginia University, Morgantown, West Virginia, USA.ORCID 0000-0001-9006-059X
West Virginia University · USCardiff University · GBInstitute of Infection and Immunity · CAUniversity of Warwick · GB

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Reagan Curtis · 2012 to 2026
$81.0M
WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI Trupti Joshi · 2012 to 2026
$61.1M
WVU Flow Cytometry and Single Cell Core Facility (FCSCCF)P20GM121322 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Rachel M. Abbotts · 2018 to 2026
$22.4M
VS-CoBRE Administrative CoreP20GM144230 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Visvanathan Ramamurthy · 2022 to 2026
$13.9M
Regulation of Tight Junction Molecular Composition by Na/K-ATPaseP20GM121299 · NIGMS · MARSHALL UNIVERSITY · PI HAYNES, JENNIFER · 2018 to 2022
$10.6M
In vivo monitoring of tumor microenvironment regulation for macrophagesR01CA194013 · NCI · WEST VIRGINIA UNIVERSITY · PI Timothy D Eubank, Valery V Khramtsov · 2015 to 2026
$3.5M
Profiling chemical tumor microenvironment: Application for diagnostics & therapyR01CA192064 · NCI · WEST VIRGINIA UNIVERSITY · PI EUBANK, TIMOTHY D, KHRAMTSOV, VALERY V · 2015 to 2024
$3.4M
Cell and Molecular Biology Training Program at West Virginia UniversityT32GM133369 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Zoica Cerasela Dinu, MICHAEL D SCHALLER · 2019 to 2026
$2.0M
NCI NIH HHS NCI R01CA192064NCI NIH HHS NCI R01CA194013NCI NIH HHS R01 CA192064NCI NIH HHS R01 CA194013NIGMS NIH HHS NIGMS 5U54GM104942-04NIGMS NIH HHS NIGMS CoBRE 5P20GM121322NIGMS NIH HHS NIGMS P20 GM103434NIGMS NIH HHS NIGMS P20 GM121322NIGMS NIH HHS NIGMS T32 GM133369NIGMS NIH HHS NIGMS U54 GM-104942NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P20 GM121299NIGMS NIH HHS P20 GM121322NIGMS NIH HHS P20 GM144230NIGMS NIH HHS T32 GM133369NIGMS NIH HHS U54 GM104942
6 · The paper itself

Abstract

backgroundA better understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment is critical to developing new treatments and improving outcomes. Myeloid cells are of particular importance for PDAC progression; however, the presence of heterogenous subsets with different ontogeny and impact, along with some fluidity between them, (infiltrating monocytes vs. tissue-resident macrophages; M1 vs. M2) makes characterisation of myeloid populations challenging. Recent advances in single cell sequencing technology provide tools for characterisation of immune cell infiltrates, and open chromatin provides source and function data for myeloid cells to assist in more comprehensive characterisation. Thus, we explore single nuclear assay for transposase accessible chromatin (ATAC) sequencing (snATAC-Seq), a method to analyse open gene promoters and transcription factor binding, as an important means for discerning the myeloid composition in human PDAC tumours.

methodsFrozen pancreatic tissues (benign or PDAC) were prepared for snATAC-Seq using 10× Chromium technology. Signac was used for preliminary analysis, clustering and differentially accessible chromatin region identification. The genes annotated in promoter regions were used for Gene Ontology (GO) enrichment and cell type annotation. Gene signatures were used for survival analysis with The Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD) dataset.

resultsMyeloid cell transcription factor activities were higher in tumour than benign pancreatic samples, enabling us to further stratify tumour myeloid populations. Subcluster analysis revealed eight distinct myeloid populations. GO enrichment demonstrated unique functions for myeloid populations, including interleukin-1b signalling (recruited monocytes) and intracellular protein transport (dendritic cells). The identified gene signature for dendritic cells influenced survival (hazard ratio = .63, p = .03) in the TCGA-PAAD dataset, which was unique to PDAC.

conclusionsThese data suggest snATAC-Seq as a method for analysis of frozen human pancreatic tissues to distinguish myeloid populations. An improved understanding of myeloid cell heterogeneity and function is important for developing new treatment targets in PDAC.

Indexed as

AdenocarcinomaCarcinoma, Pancreatic DuctalPancreatic NeoplasmsChromatinHumansTranscription FactorsTumor MicroenvironmentChromatinTranscription FactorsATAC-SeqmyeloidPDAC

Identifiers

PMID38426634
PMCPMC10905544
OpenAlexW4392366622

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.