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Cell death analysis of inducible, titratable neurodegenerative disease models in zebrafish and human stem cell-derived retinal organoids.

Code ↔ Paper

3 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 3 matches
  1. [1] § MATERIALS AND METHODS › Transcriptomic data processing ↔ preprocessing_basics.ipynb, lines 208–237 · score 0.54 · highly variable genes, filtered, apoptosis, necroptosis, parthanatos
  2. [2] § MATERIALS AND METHODS › Cell death pathway scoring ↔ time_course.ipynb, lines 234–346 · score 0.53 · sham signatures, baseline, Scanpy, score, gene
  3. [3] § RESULTS › Cell death signatures in transcriptomic datasets of NTR 2.0/MTZ-based ablation ↔ time_course.ipynb, lines 234–346 · score 0.51 · gene signature, sham signatures, ablated, signaling, score, apoptosis

Paper

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The authors' code

Jupyter notebook · 647 lines · 30 KB · no license · 2 matches

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Overview

Authors: Anneliese Ceisel1, Gianna Graziano1, Kevin Emmerich1,2, Xiangqian Shi1,3, Tae-In Kam4,5, Miguel Flores-Bellver6, M. Natalia Vergara6, Silvia Aparicio-Domingo6, Boris M. Brenerman7, Anne Vielle6, Elsie M. Williams8,9, Abigail V. Sharrock8,9, Uche Onuchuwku1, Georgina S. Martinez1, Lydia G. Sanders1, Uzoamaka Nwagbo10, Beichen Wang10, Huanhuan Xiao1, Grant Kroeschell1, Yiqi Gao1
and 16 other authorsDaniel J. Choe1, Caroline E. Clouatre1, Diego Alfaro Carcoba1, Barak Reibman1, Catalina Rodriguez1, Kevin Yang1, Shreya Banerjee1, Frazer Matthews1, James H. Thierer1, Genevieve Stein-O'Brien7, Ted M. Dawson4,5,7,11, Valina L. Dawson4,5,7,11, David F. Ackerley8,9, M. Valeria Canto-Soler2, Liyun Zhang1,10, Jeff S. Mumm1,7
ORCID iDs: Grant Kroeschell, David F. Ackerley, Liyun Zhang, Jeff S. Mumm
  1. Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
  2. Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20814, USA
  3. Department of Pharmaceutical Sciences, University of Illinois-Chicago, Chicago, IL 60612, USA
  4. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  5. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  6. CellSight Ocular Stem Cell and Regeneration Research Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado Anschutz, Aurora, CO 80045, USA
  7. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  8. School of Biological Sciences, Victoria University of Wellington. Wellington 6140, New Zealand
  9. Te Matapihipihi - The Centre for Biodiscovery and Maurice Wilkins Centre for Molecular Biodiscovery, Victoria University of Wellington, Wellington 6140, New Zealand
  10. Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15219, USA
  11. Department of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Institutions: Johns Hopkins University (United States); Johns Hopkins Medicine (United States); National Institutes of Health (United States); National Heart, Lung, and Blood Institute (United States); University of Illinois Chicago (United States); University of Colorado Anschutz (United States); Victoria University of Wellington (New Zealand); University of Pittsburgh (United States)
Journal: Disease models & mechanisms, volume 19, issue 7, article dmm052747
Dates: received 6 November 2025; accepted 12 June 2026; published online 24 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1242/dmm.052747 · PMID 42497345 · PMCID PMC13474575 · OpenAlex W7170874272
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), zebrafish (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, fMRI & imaging
Keywords: Cell death, Nitroreductase, Parthanatos, Inducible disease model, Neurodegeneration, Retinal organoids
MeSH: Neurodegenerative Diseases*, Organoids*, Retina*, Stem Cells*, Zebrafish*, Animals, Apoptosis, Cell Death, Disease Models, Animal, Humans, Metronidazole, Nitroreductases (* major topic)
Topic: Retinal Development and Disorders (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Eye Institute (F31:EY032790, P30:EY1765, R01:EY033009, R01:EY032533, R01:OD020376, T32:EY7143-22, F31:EY037171); Maryland Department of Commerce; Dr. Ralph and Marian Falk Medical Research Trust; Marsden Fund (VUW2402, VUW1902); CellSight Development Fund; Research to Prevent Blindness, Inc; Doni Solich Family Chair in Ocular Stem Cell Research; BrightFocus Foundation (BrightFocus) (M2024008N); Foundation Fighting Blindness; Johns Hopkins University; School of Medicine, Johns Hopkins University
Citations: not cited yet (Europe PMC); 119 references in the paper

Abstract

Inducible disease models enable large-scale screening by providing control over pathology onset, such as cell death in neurodegenerative disease. The nitroreductase (NTR)/prodrug system of cell ablation has facilitated investigations of cell function and regeneration but has not been widely adopted as a disease modeling platform, perhaps owing to assumptions that the cell death mechanism(s) elicited is artificial in nature. Prior reports suggested that NTR/prodrug-mediated death occurred through apoptosis, necroptosis and/or parthanatos, which have all been implicated in neurodegenerative disease. To clarify this issue, we investigated the cell death pathway(s) elicited by the prodrug metronidazole (MTZ) with improved nitroreductase enzyme variants. We assessed the cell death pathway(s) elicited by NTR 2.0-expressing zebrafish retinal neurons using a transcriptomic analysis, chemical inhibitors and gene-targeting assays. NTR-H, a novel NTR variant, was tested – and found to be effective – in human stem cell-derived retinal organoids. Parthanatos was implicated across all conditions tested, while evidence of apoptosis was variable. As parthanatos is associated with neurodegeneration, our results support the use of the NTR/MTZ system to create inducible neurodegenerative models targeted to specific disease-relevant neuronal cell types.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above, with 3 matches between paragraphs and lines of code.

mummlab/Cell-Death-in-NTR2.0-mediated-RGC-Ablation

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 900c21f8408c85500dc5d06df62160866ba0c181, 12 May 2026
Languages: Jupyter (4), Python (1)
Size: 10 files, 5 scripts
Software Heritage: not archived
Found in: the end of the paper
Holds: README, environment (envs/env.yml), 4 notebooks
Not found: license file, CITATION.cff, tests, continuous integration, documentation
Tools: Matplotlib (5 files), NumPy (5 files), pandas (4 files), Scanpy (4 files), SciPy (4 files), anndata (2 files), scikit-learn (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
6 files, not copied: shown from their source

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At the source: github.com/mummlab/Cell-Death-in-NTR2.0-mediated-RGC-Ablation

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 5 scripts, each with its path and the digest of its content;
  • 3 matches between paragraphs of the paper and lines of the code (method lexical-v1);
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 36 authors, 6 keywords, 12 MeSH terms, 11 funders, 119 references.

Cite

This paper

Ceisel, A., Graziano, G., Emmerich, K., Shi, X., Kam, T.-I., Flores-Bellver, M., Vergara, M. N., Aparicio-Domingo, S., Brenerman, B. M., Vielle, A., Williams, E. M., Sharrock, A. V., Onuchuwku, U., Martinez, G. S., Sanders, L. G., Nwagbo, U., Wang, B., Xiao, H., Kroeschell, G., . . . Mumm, J. S. (2026). Cell death analysis of inducible, titratable neurodegenerative disease models in zebrafish and human stem cell-derived retinal organoids. Disease models & mechanisms, 19(7), dmm052747. https://doi.org/10.1242/dmm.052747

BibTeX

@article{ceisel2026cell,
author = {Ceisel, Anneliese and Graziano, Gianna and Emmerich, Kevin and Shi, Xiangqian and Kam, Tae-In and Flores-Bellver, Miguel and Vergara, M. Natalia and Aparicio-Domingo, Silvia and Brenerman, Boris M. and Vielle, Anne and Williams, Elsie M. and Sharrock, Abigail V. and Onuchuwku, Uche and Martinez, Georgina S. and Sanders, Lydia G. and Nwagbo, Uzoamaka and Wang, Beichen and Xiao, Huanhuan and Kroeschell, Grant and Gao, Yiqi and Choe, Daniel J. and Clouatre, Caroline E. and Carcoba, Diego Alfaro and Reibman, Barak and Rodriguez, Catalina and Yang, Kevin and Banerjee, Shreya and Matthews, Frazer and Thierer, James H. and Stein-O'Brien, Genevieve and Dawson, Ted M. and Dawson, Valina L. and Ackerley, David F. and Canto-Soler, M. Valeria and Zhang, Liyun and Mumm, Jeff S.},
title = {{Cell death analysis of inducible, titratable neurodegenerative disease models in zebrafish and human stem cell-derived retinal organoids}},
journal = {Disease models \& mechanisms},
year = {2026},
month = jul,
volume = {19},
number = {7},
pages = {dmm052747},
publisher = {Company of Biologists},
issn = {1754-8403},
doi = {10.1242/dmm.052747},
url = {https://doi.org/10.1242/dmm.052747},
pmid = {42497345},
pmcid = {PMC13474575}
}

RIS

TY - JOUR
AU - Ceisel, Anneliese
AU - Graziano, Gianna
AU - Emmerich, Kevin
AU - Shi, Xiangqian
AU - Kam, Tae-In
AU - Flores-Bellver, Miguel
AU - Vergara, M. Natalia
AU - Aparicio-Domingo, Silvia
AU - Brenerman, Boris M.
AU - Vielle, Anne
AU - Williams, Elsie M.
AU - Sharrock, Abigail V.
AU - Onuchuwku, Uche
AU - Martinez, Georgina S.
AU - Sanders, Lydia G.
AU - Nwagbo, Uzoamaka
AU - Wang, Beichen
AU - Xiao, Huanhuan
AU - Kroeschell, Grant
AU - Gao, Yiqi
AU - Choe, Daniel J.
AU - Clouatre, Caroline E.
AU - Carcoba, Diego Alfaro
AU - Reibman, Barak
AU - Rodriguez, Catalina
AU - Yang, Kevin
AU - Banerjee, Shreya
AU - Matthews, Frazer
AU - Thierer, James H.
AU - Stein-O'Brien, Genevieve
AU - Dawson, Ted M.
AU - Dawson, Valina L.
AU - Ackerley, David F.
AU - Canto-Soler, M. Valeria
AU - Zhang, Liyun
AU - Mumm, Jeff S.
TI - Cell death analysis of inducible, titratable neurodegenerative disease models in zebrafish and human stem cell-derived retinal organoids
T2 - Disease models & mechanisms
J2 - Dis Model Mech
PY - 2026
DA - 2026/07/24
VL - 19
IS - 7
SP - dmm052747
SN - 1754-8403
PB - Company of Biologists
DO - 10.1242/dmm.052747
UR - https://doi.org/10.1242/dmm.052747
LA - en
ER -

CSL-JSON

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