Evidence map›Paper›PMID 40359937›Full record

ArticleCell reports methods2025

Harmonizing TUNEL with multiplexed iterative immunofluorescence enriches spatial contextualization of cell death.

Marc S Sherman, Thomas McMahon-Skates, Lindsey S Gaston, Sonya W Katzen, Joseph A Majzoub, Wolfram Goessling

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

6 authors.

Marc S ShermanDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: msherman@mgh.harvard.edu.
Thomas McMahon-SkatesDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lindsey S GastonDivision of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Sonya W KatzenDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Joseph A MajzoubDivision of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Wolfram GoesslingDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. Electronic address: wgoessling@mgh.harvard.edu.

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JERROLD R. TURNER · 1986 to 2026
$32.4M
RESEARCH TRAINING IN DIGESTIVE DISEASES AND NUTRITIONT32DK007191 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1986 to 2026
$14.6M
A Community Zebrafish Resource for Modeling GWAS BiologyR24OD017870 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI GOESSLING, WOLFRAM, MACRAE, CALUM A. · 2014 to 2021
$6.3M
Estrogen Regulation of Hepatic GrowthR01DK090311 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GOESSLING, WOLFRAM · 2011 to 2020
$4.9M
Metabolic Regulation of Liver GrowthR01DK105198 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GOESSLING, WOLFRAM · 2016 to 2020
$2.7M
Dysregulation of the unfolded protein response in the pathogenesis of non-alcoholic steatohepatitisK08DK139370 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARC S SHERMAN · 2025 to 2026
$342k
Suppression and Recovery of the Murine Hypothalamic-Pituitary-Adrenal Axis after Exogenous Glucocorticoid TreatmentF32DK131795 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI GASTON, LINDSEY SARA · 2021 to 2023
$156k
NIDDK NIH HHS F32 DK131795NIDDK NIH HHS K08 DK139370NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK090311NIDDK NIH HHS R01 DK105198NIDDK NIH HHS T32 DK007191NIH HHS R24 OD017870
6 · The paper itself

Abstract

Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) is an essential tool for detecting cell death in tissues, but its compatibility with spatial proteomic methods is unknown. We evaluated variations of the TUNEL protocol for compatibility with multiple iterative labeling by antibody neodeposition (MILAN) in acetaminophen-induced hepatocyte necrosis and dexamethasone-induced adrenocortical apoptosis. Using a commercial Click-iT-based assay as a standard, TUNEL signal could be reliably produced independent of the antigen retrieval method, with tissue-specific minor differences in signal to noise. In contrast, proteinase K treatment consistently reduced or even abrogated protein antigenicity, while pressure cooker treatment enhanced protein antigenicity for the targets tested. Antibody-based TUNEL with pressure cooker retrieval could be flexibly integrated into a MILAN staining series, and first-round TUNEL was also compatible with a second spatial proteomic method, cyclic immunofluorescence (CycIF). We anticipate that this harmonization of TUNEL with spatial proteomics will enhance the spatial contextualization of cell death in complex tissues.

Indexed as

Fluorescent Antibody TechniqueIn Situ Nick-End LabelingAcetaminophenAnimalsApoptosisCell DeathDexamethasoneHepatocytesHumansNecrosisProteomicsAcetaminophenDexamethasoneacetaminophen liver toxicityapoptosiscell deathCP: ImagingCycIFdexamethasone-induced adrenal insufficiencyMILANproteinase Kspatial proteomicsTUNELzonation

Identifiers

PMID40359937
PMCPMC12146639

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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 OpenQuestion graph.