Cellular and Axonal Transport Phenotypes Due to the C9ORF72 HRE in IPSC Motor and Sensory Neurons

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2024 Jun 14

PMID 38876108

Authors

Jakub Scaber

Iona Thomas-Wright

Alex J Clark

Yinyan Xu

Bjorn F Vahsen

Mireia Carcole

Ruxandra Dafinca

Lucy Farrimond

Adrian M Isaacs

David L Bennett

Kevin Talbot

Affiliations

Soon will be listed here.

Abstract

Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.

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