OSCR

Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer's disease.

Overview

Authors: Wenzhe Wu1, Eun Seok Choi1, Luke Liu2,3, Veena Thamilselvan3, Le Li4, Meagan D. Rippee-Brooks1, Kashish Khatkar1, Dar-Yin Li1, Denise McGrath5, Aidan Manning5, Sergio Barberan-Soler5, Inhan Lee3, Yingxin Zhao6, Xiang Fang7,8,9, Xiaoyong Bao1,9,10
ORCID iDs: Eun Seok Choi
  1. Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States
  2. Department of Computer Science, University of Rochester, Rochester, NY, United States
  3. miRcore, Ann Arbor, MI, United States
  4. Department of Mathematics, College of Natural Sciences, The University of Texas at Austin, Austin, TX, United States
  5. RealSeq Biosciences, Santa Cruz, CA, United States
  6. Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States
  7. Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States
  8. Moody Brain Health Institute, University of Texas Medical Branch, Galveston, TX, United States
  9. Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, United States
  10. Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX, United States
Institutions: The University of Texas Medical Branch at Galveston (United States); MIRCORE; University of Rochester (United States); The University of Texas at Austin (United States)
Journal: Frontiers in neuroscience, volume 20, article 1799542
Dates: received 29 January 2026; accepted 24 April 2026; published online 26 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3389/fnins.2026.1799542 · PMID 42273366 · PMCID PMC13246725 · OpenAlex W7162458319
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Machine learning, Connectivity
Keywords: Alzheimer’s disease, iPSC-derived microglia (iMG), multiple omics, T4 PNK-sncRNA-seq, tRNA-derived RNA fragment (tRF)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Citations: not cited yet (Europe PMC); 94 references in the paper

Abstract

Introduction: Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining neural homeostasis and regulating inflammatory responses in the brain. Increasing evidence suggests that microglial dysfunction contributes to the progression of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the molecular mechanisms underlying these alterations remain incompletely understood. This study aimed to characterize disease-associated molecular changes in microglia derived from induced pluripotent stem cells (iPSCs) of sporadic AD patients and healthy donors.

Methods: iPSC-derived microglia from sporadic AD patients and healthy controls were analyzed using integrated multi-omics approaches, including total RNA sequencing, proteomics, and small non-coding RNA (sncRNA) sequencing. Gene Ontology (GO) analysis was performed to identify dysregulated biological pathways from transcriptomic and proteomic datasets. In addition, a modified T4 polynucleotide kinase (T4 PNK)-based sncRNA sequencing method was used to profile disease-associated sncRNAs and identify previously uncharacterized RNA species.

Results: Comparative analyses revealed significant AD-associated alterations in mRNA, protein, and sncRNA expression profiles in iPSC-derived microglia. GO analysis demonstrated dysregulation of pathways related to extracellular communication, intracellular transport, cytoskeletal organization, and protein–protein interactions. Furthermore, the modified T4 PNK–sncRNA sequencing approach identified multiple disease-associated sncRNAs, including several novel and previously uncharacterized RNA species potentially linked to AD pathology.

Discussion: These findings demonstrate that iPSC-derived microglia provide a valuable model for studying molecular mechanisms associated with sporadic AD. The identified transcriptomic, proteomic, and sncRNA alterations highlight key pathways potentially involved in microglial dysfunction and neurodegeneration. In particular, the discovery of novel disease-associated sncRNAs may provide new insights into AD pathogenesis and reveal potential therapeutic targets for future investigation.

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.

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Data

Datasets cited

Data availability statement

The original contributions presented in the study are publicly available, and are available in the Supplementary material. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332551.

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, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 15 authors, 5 keywords, 94 references.

Cite

This paper

Wu, W., Choi, E. S., Liu, L., Thamilselvan, V., Li, L., Rippee-Brooks, M. D., Khatkar, K., Li, D.-Y., McGrath, D., Manning, A., Barberan-Soler, S., Lee, I., Zhao, Y., Fang, X., & Bao, X. (2026). Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer's disease. Frontiers in neuroscience, 20, 1799542. https://doi.org/10.3389/fnins.2026.1799542

BibTeX

@article{wu2026disease,
author = {Wu, Wenzhe and Choi, Eun Seok and Liu, Luke and Thamilselvan, Veena and Li, Le and Rippee-Brooks, Meagan D. and Khatkar, Kashish and Li, Dar-Yin and McGrath, Denise and Manning, Aidan and Barberan-Soler, Sergio and Lee, Inhan and Zhao, Yingxin and Fang, Xiang and Bao, Xiaoyong},
title = {{Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer's disease}},
journal = {Frontiers in neuroscience},
year = {2026},
month = may,
volume = {20},
pages = {1799542},
publisher = {Frontiers Media SA},
issn = {1662-4548},
doi = {10.3389/fnins.2026.1799542},
url = {https://doi.org/10.3389/fnins.2026.1799542},
pmid = {42273366},
pmcid = {PMC13246725}
}

RIS

TY - JOUR
AU - Wu, Wenzhe
AU - Choi, Eun Seok
AU - Liu, Luke
AU - Thamilselvan, Veena
AU - Li, Le
AU - Rippee-Brooks, Meagan D.
AU - Khatkar, Kashish
AU - Li, Dar-Yin
AU - McGrath, Denise
AU - Manning, Aidan
AU - Barberan-Soler, Sergio
AU - Lee, Inhan
AU - Zhao, Yingxin
AU - Fang, Xiang
AU - Bao, Xiaoyong
TI - Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer's disease
T2 - Frontiers in neuroscience
J2 - Front Neurosci
PY - 2026
DA - 2026/05/26
VL - 20
SP - 1799542
SN - 1662-4548
PB - Frontiers Media SA
DO - 10.3389/fnins.2026.1799542
UR - https://doi.org/10.3389/fnins.2026.1799542
LA - en
ER -

CSL-JSON

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