PXD070094-1

PXD070094 is an original dataset announced via ProteomeXchange.

Title	Time-resolved multi-omic analysis of paclitaxel exposure in human iPSC-derived sensory neurons unveils mechanisms of chemotherapy-induced peripheral neuropathy
Description	The microtubule-stabilizing drug paclitaxel remains standard of care for various solid malignancies but frequently leads to chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a leading cause for premature treatment termination and a significantly reduced quality of life in long-term cancer survivors. The molecular mechanisms of neuro-axonal degeneration, neuroinflammation and pain in patients treated with paclitaxel remain incompletely understood, and there are currently no predictive biomarkers or preventive treatments. We used human iPSC-derived sensory neurons exposed to paclitaxel to comprehensively model the pathophysiology of CIPN. Neurotoxicity was assessed over time using viability assays and sequential RNA sequencing as well as deep proteome and lipidomic analyses. We observed a time and dose-dependent decline of cell viability at clinically relevant paclitaxel doses. Sequential RNA sequencing defined JUN as an early immediate gene, followed by the overexpression of genes of the neuronal stress response (e.g., ARID5A, WEE1, DUSP16, GADD45A), neuronal injury and apoptotic pathways (e.g., ATF3, HRK, BBC3 [PUMA], BCL2L11 [BIM], CASP3), neuroinflammation and nociception (CALCB, MMP10, IL31RA, CYSLTR2, C3AR1, TNFRSF12A) and neuronal transduction (e.g., CAMK2A, STOML3), while key enzymes of lipid biosynthesis were markedly downregulated (e.g., LSS, HMGCS1, HMGCR, DHCR24). Deep proteome analyses following 48 hours of exposure to 100nM paclitaxel revealed a strong correlation of differentially expressed RNA with proteins, and a marked degradation of essential axonal transport proteins such as kinesins, stathmins and scaffold proteins. Consistent with the downregulation of rate-limiting enzymes of lipid biosynthesis, lipidome analysis confirmed deregulation of neuronal lipid homeostasis. In summary, paclitaxel induces transcriptomic and proteomic signatures of the neuronal stress response, neuroinflammation, nociception and disturbed metabolism. These may explain, in part, the clinical phenotype of sensory loss, hypersensitivity and neuropathic pain frequently observed in patients suffering from CIPN, but constitute pharmacologically addressable targets
HostingRepository	PRIDE
AnnounceDate	2026-02-22
AnnouncementXML	Submission_2026-02-22_11:36:52.002.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-30 06:03:13	ID requested
⏵ 1	2026-02-22 11:36:52	announced

10.1038/S41419-026-08445-2;

submitter keyword: chemotherapy-induced peripheral neuropathy, neuroinflammation, pain, TMT, human,Induced pluripotent stem cell-derived sensory neurons , paclitaxel, neurodegeneration

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charite-Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany
contact email	Philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070094
     1. Label: PRIDE project
     2. Name: Time-resolved multi-omic analysis of paclitaxel exposure in human iPSC-derived sensory neurons unveils mechanisms of chemotherapy-induced peripheral neuropathy