Canonical autophagy remains inactive in induced pluripotent stem cells and neuronal progenitor cells following DNA damage induced by BPDE or etoposide.

Overview

1. Institute of Molecular Medicine I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University,Universitätsstr. 1, Building 22.03, 40225 Düsseldorf, Germany
2. Molecular Proteomics Laboratory, Biological Medical Research Center, Heinrich Heine University Düsseldorf,40225 Düsseldorf, Germany
3. Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University,40225 Düsseldorf, Germany

Abstract

(Macro-)Autophagy is a key cellular stress response mediating the recycling of long-lived or damaged proteins and organelles. In stem cells, autophagy is essential for the decision between quiescence, self-renewal and differentiation. We observed that induced pluripotent stem cells (iPSCs) and thereof derived neural progenitor cells (NPCs) have a functional autophagy machinery, as shown by starvation-induced autophagic flux and ULK1 activation. Using the human iPSC lines iPS11 and iPS12 and thereof derived NPCs (niPS11 and niPS12), we investigated whether genotoxic stress induced by low doses (IC20) of benzo[a]pyrene diolepoxide (BPDE) or etoposide can similarly activate autophagy, as previously reported for cancer cell lines. While both BPDE and etoposide induced the DNA damage markers phospho-p53 Ser15 and γH2AX and slightly altered the expression of DNA repair proteins such as XPC, they did not trigger autophagic flux in either iPSCs or NPCs. After genotoxin treatment, ULK1 activation was only observed in NPCs, but this was not sufficient to trigger a significant downstream autophagic response. Mass spectrometry revealed minimal proteomic changes in iPSCs and moderate changes in NPCs, mainly involving mitotic regulators. In summary, no significant activation of canonical autophagy was detectable in iPSCs and NPCs within the tested time frame and under low-dose genotoxic conditions, although both cell types retain a functional autophagic machinery.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-54127-6.

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

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• uniprot.org/uniprotkb, at UniProt; found in “Data availability”

Data availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE60 partner repository with the dataset identifier PXD066480 and can be accessed here: https://www.ebi.ac.uk/pride/archive?keyword=PXD066480. The fasta files containing the protein sequence databases (downloaded on 12/21/2023 for the MaxQuant search or on 07/08/2024 for the DIA-NN search; present link: https://www.uniprot.org/uniprotkb?query=(proteome%3AUP000005640) (https://www.uniprot.org/uniprotkb?query=(proteome:UP000005640))) are provided with these proteomics data. Further information and requests for resources and reagents should be directed to and will be fulfilled by the corresponding author, Björn Stork.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 9 keywords, 9 MeSH terms, 1 funder, 60 references.

Cite

This paper

Akgün, S., Naren, P., Lenz, T., Zink, A., Krings, K. S., Wesselborg, S., Mendiburo, M. J., Prigione, A., Stühler, K., & Stork, B. (2026). Canonical autophagy remains inactive in induced pluripotent stem cells and neuronal progenitor cells following DNA damage induced by BPDE or etoposide. Scientific reports, 16(1), 18028. https://doi.org/10.1038/s41598-026-54127-6

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1007/s12640-026-00825-y

Atorvastatin Shows Limited Disease-Modifying Effects in an A53T α-Synuclein Mouse Model of Parkinson's Disease.

Journal: Neurotoxicity research

In common: uniprot.org/uniprotkb, cellular / molecular

[2] doi:10.3390/cells15151379

Extracellular Aβ42 Oligomers Induce ROCK2 Hyperactivation Through Dual Mediation by RhoA and GzmB: Significance of Moderate ROCK2 Activity in Neural Cells.

Journal: Cells

In common: uniprot.org/uniprotkb, cellular / molecular

[3] doi:10.1007/s10571-026-01706-w

Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy.

Journal: Cellular and molecular neurobiology

In common: uniprot.org/uniprotkb, cellular / molecular

[4] doi:10.1093/nar/gkag621 [code]

Optimal gene panel selection for targeted spatial transcriptomics experiments.

Journal: Nucleic acids research

In common: cellular / molecular, 2 references

[5] doi:10.1111/bpa.70125

From patient to tumor organoid: Culture protocol choice controls glioblastoma tumor architecture and identity.

Journal: Brain pathology (Zurich, Switzerland)

In common: other condition, 2 references

[6] doi:10.1126/sciadv.aea8940 [code]

Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment.

Journal: Science advances

In common: cellular / molecular, 2 references

[7] doi:10.1038/s41467-026-71418-8 [code]

Deep visual proteomics uncovers nociceptor diversity and pain targets.

Journal: Nature communications

In common: cellular / molecular, 2 references

[8] doi:10.3390/biom16050621

Calretinin and Parvalbumin Trapping of TDP43 and XRCC1 Instructs Neocortical Interneuron Death in Neonatal Hypoxic-Ischemic Encephalopathy.

Journal: Biomolecules

In common: other condition, 1 reference

[9] doi:10.1242/bio.062414

Autophagic flux blockade under hypocapnia reveals CO2-sensitive regulation of autophagy-lysosome homeostasis.

Journal: Biology open

In common: cellular / molecular, 1 reference

[10] doi:10.1016/j.nbd.2026.107379 [code]

DYRK1A and Parkinson's disease, facts and hypotheses.

Journal: Neurobiology of disease

In common: cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.