Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity.

ABSTRACT:

Background

Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained.

Results

Analyzing single-cell RNA sequencing from Alzheimer's disease (AD) and Huntington's disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons. We hypothesize that transcriptional heterogeneity precedes neurodegenerative disease pathologies. To test this idea experimentally, we use juvenile forms (72Q; 180Q) of HD iPSCs, differentiate them into committed neuronal progenitors, and obtain single-cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy gene

SUBMITTER: Sorek M 

PROVIDER: S-EPMC7934477 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature