An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients
Name
1-s2.0-S2589004221011895-main.pdf
Description
Published version
Size
11.7 MB
Format
Adobe PDF
Checksum (MD5)
d768da581a6defc4de1467111c2f62f6
Author(s)
Fraenkel, Ernest
Date Issued
2021
Journal
iScience
Publisher
Elsevier BV
Citation
Fraenkel, Ernest. 2021. "An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients." iScience, 24 (11).
Version
Final published version
Abstract
Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.ISCI.2021.103221
