IPSC motor neurons, but not other derived cell types, capture gene expression changes in postmortem sporadic ALS motor neurons.

ABSTRACT: Motor neuron degeneration, the defining feature of amyotrophic lateral sclerosis (ALS), is a primary example of cell-type specificity in neurodegenerative diseases. Using isogenic pairs of induced pluripotent stem cells (iPSCs) harboring different familial ALS mutations, we assess the capacity of iPSC-derived lower motor neurons, sensory neurons, astrocytes, and superficial cortical neurons to capture disease features including transcriptional and splicing dysregulation observed in human postmortem neurons. At early time points, differentially regulated genes in iPSC-derived lower motor neurons, but not other cell types, overlap with one-third of the differentially regulated genes in laser-dissected motor neurons from ALS compared with control postmortem spinal cords. For genes altered in

SUBMITTER: Held A 

PROVIDER: S-EPMC10622181 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature