Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls

Bibliographic Details
Title: Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls
Authors: Stanislav Tsitkov, Kelsey Valentine, Velina Kozareva, Aneesh Donde, Aaron Frank, Susan Lei, the Answer ALS Consortium, Jennifer E. Van Eyk, Steve Finkbeiner, Jeffrey D. Rothstein, Leslie M. Thompson, Dhruv Sareen, Clive N. Svendsen, Ernest Fraenkel
Source: Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)
Publisher Information: Nature Portfolio, 2024.
Publication Year: 2024
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-024-47758-8
Access URL: https://doaj.org/article/99c7b8055b0b402a8beedb66a340ca58
Accession Number: edsdoj.99c7b8055b0b402a8beedb66a340ca58
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-024-47758-8
Published in:Nature Communications
Language:English