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Convergent transcriptomic signature in iPSC-dopaminergic neurons of hereditary Parkinson's disease.

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License · 21 lines · 1 KB · MIT

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LICENSE at commit 34c7269, under MIT · at the source

Overview

Authors: Irina V Kopylova1,2, Artem B Ivanov1,3, Lev R Eidelman3, Ekaterina N Zaitseva3, Ekaterina D Kulikova3, Dmitriy A Grehnyov4, Alexandra N Bogomazova1,2, Vladimir A Vigont4, Elena V Kaznacheyeva4, Maria A Lagarkova1,2, Olga S Lebedeva1,2, Evgenii I Olekhnovich1,2
ORCID iDs: Irina V Kopylova, Lev R Eidelman, Ekaterina D Kulikova, Dmitriy A Grehnyov, Maria A Lagarkova, Olga S Lebedeva, Evgenii I Olekhnovich
  1. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, of Federal Medical Biological Agency, Moscow, Russia
  2. Center for Genetic Reprogramming and Gene Therapy, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, of Federal Medical Biological Agency, Moscow, Russia
  3. ITMO University, St. Petersburg, Russia
  4. Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia
Institutions: Federal Research and Clinical Center of Physical-Chemical Medicine named after Y.M. Lopukhin (Russia); ITMO University (Russia); Institute of Cytology (Russia)
Journal: Life science alliance, volume 9, issue 7, article e202503551
Dates: received 28 October 2025; accepted 27 March 2026; published online 24 April 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.26508/lsa.202503551 · PMID 42031673 · PMCID PMC13109591 · OpenAlex W7155529311
Open access: gold, a free copy (OpenAlex)
Status: empty repository
Categories: genetics / omics (modality), human (organism), Parkinson's (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, fMRI & imaging
MeSH: Dopaminergic Neurons*, Induced Pluripotent Stem Cells*, Parkinson Disease*, Transcriptome*, Cell Differentiation, Gene Expression Profiling, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mutation, Ubiquitin-Protein Ligases (* major topic)
Topic: Parkinson's Disease Mechanisms and Treatments (Neurology, Medicine), according to OpenAlex
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

The clinical and genetic diversity of Parkinson’s disease (PD) makes it challenging to identify common mechanisms across different forms. To search for such shared pathways, we performed transcriptomic analysis of iPSC-derived dopaminergic neurons from patients with LRRK2 or Parkin mutations. We discovered a convergent gene expression signature in both genetic backgrounds, indicating a shift away from developmental and proliferative programs (e.g., Wnt/β-catenin signaling, cell cycle) and toward pathways of mature neuronal function (e.g., synaptic transmission, potassium channels). This shift was particularly pronounced in LRRK2 neurons, which showed enhanced markers of synaptic maturation. Concurrently, PD neurons exhibited down-regulation of gene programs supporting axon growth and structural development and upregulated TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway. Our findings suggest that in these hereditary forms of PD, distinct mutations may propel neurons toward a similar state of premature specialization coupled with impaired structural development and increased vulnerability, revealing a potential common path in disease pathogenesis.

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

Repository

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cbio-lab/PARK2023

License: MIT
State: the link answers, verified on 30 September 2026
Evidence: files inventoried
Commit: 34c72695cf957cb636e06d6b92d9f622946799b3, 16 July 2026
Size: 5 files, 0 scripts
Software Heritage: not archived
Found in: “Data Availability”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 30 September 2026: the link answers
  • 30 September 2026: the link answers
2 files
At the source: github.com/cbio-lab/PARK2023

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data Availability

Raw sequencing data from this study have been deposited in the NCBI SRA under BioProject ID PRJNA1346308 (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1346308). This dataset comprises 34 transcriptomes of iPSC-derived neuronal lines from PD patients and healthy controls, sequenced using Illumina NovaSeq 6000. Signatures for neuronal progenitors and mature neurons were defined based on the analysis of public RNA-seq data (GEO: GSE120271 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120271)), which profiles cells across different stages of neuronal differentiation. All custom code used for transcriptomic processing and analysis has been deposited in the GitHub repository at https://github.com/cbio-lab/PARK2023.

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

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 10 MeSH terms, 59 references.

Cite

This paper

Kopylova, I. V., Ivanov, A. B., Eidelman, L. R., Zaitseva, E. N., Kulikova, E. D., Grehnyov, D. A., Bogomazova, A. N., Vigont, V. A., Kaznacheyeva, E. V., Lagarkova, M. A., Lebedeva, O. S., & Olekhnovich, E. I. (2026). Convergent transcriptomic signature in iPSC-dopaminergic neurons of hereditary Parkinson's disease. Life science alliance, 9(7), e202503551. https://doi.org/10.26508/lsa.202503551

BibTeX

@article{kopylova2026convergent,
author = {Kopylova, Irina V and Ivanov, Artem B and Eidelman, Lev R and Zaitseva, Ekaterina N and Kulikova, Ekaterina D and Grehnyov, Dmitriy A and Bogomazova, Alexandra N and Vigont, Vladimir A and Kaznacheyeva, Elena V and Lagarkova, Maria A and Lebedeva, Olga S and Olekhnovich, Evgenii I},
title = {{Convergent transcriptomic signature in iPSC-dopaminergic neurons of hereditary Parkinson's disease}},
journal = {Life science alliance},
year = {2026},
month = apr,
volume = {9},
number = {7},
pages = {e202503551},
publisher = {Life Science Alliance LLC},
issn = {2575-1077},
doi = {10.26508/lsa.202503551},
url = {https://doi.org/10.26508/lsa.202503551},
pmid = {42031673},
pmcid = {PMC13109591}
}

RIS

TY - JOUR
AU - Kopylova, Irina V
AU - Ivanov, Artem B
AU - Eidelman, Lev R
AU - Zaitseva, Ekaterina N
AU - Kulikova, Ekaterina D
AU - Grehnyov, Dmitriy A
AU - Bogomazova, Alexandra N
AU - Vigont, Vladimir A
AU - Kaznacheyeva, Elena V
AU - Lagarkova, Maria A
AU - Lebedeva, Olga S
AU - Olekhnovich, Evgenii I
TI - Convergent transcriptomic signature in iPSC-dopaminergic neurons of hereditary Parkinson's disease
T2 - Life science alliance
J2 - Life Sci Alliance
PY - 2026
DA - 2026/04/24
VL - 9
IS - 7
SP - e202503551
SN - 2575-1077
PB - Life Science Alliance LLC
DO - 10.26508/lsa.202503551
UR - https://doi.org/10.26508/lsa.202503551
LA - en
ER -

CSL-JSON

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