Gene expression analysis in oligodendrocyte lineage

ABSTRACT: In young animals, oligodendrocyte progenitor cells (OPCs) undergo robust differentiation, progressing through stages to become pre-myelinating oligodendrocytes (Pre-OL) and ultimately myelinating oligodendrocytes (OLs). However, OPCs in aged animals are limited in their differentiation ability. This disrupts myelin maintenance in the central nervous system (CNS), leading to a lack of remyelination following demyelination injury, and eventual loss of brain function. To uncover novel factors essential for restoring resilience in aged OPCs, we employed a data-driven approach. Our approach involved the development of a computational pipeline, gSWITCH (accessible at: https://altoslabs.shinyapps.io/gSWITCH/, https://github.com/Tanay-math/gSWITCH), adept at capturing precise dynamic gene expression patterns to pinpoint potential 'switch' genes during lineage progression, including transcription factors. By identifying this set of potential switch genes crucial for OPCs, we conducted a comparative analysis of gene expression between young and aged animals. This revealed a group of transcription factors (in switches) exhibiting downregulation in aged OPCs. Further analysis of transcription factor binding site enrichment in OPC switches highlighted Bcl11a, a zinc finger transcription factor that could potentially serve as a master regulator of many switch genes. Ectopic overexpression of Bcl11a in aged OPCs did not enhance their proliferation; however, significantly enhanced their differentiation into OLs. Furthermore, overexpression of Bcl11a in aged mice, followed by demyelination injury in the spinal cord, significantly increased the differentiation of OPCs into OLs within the injury region compared to control aged mice. These findings suggest that Bcl11a expression in OPCs restores their differentiation potential.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE301578 | GEO | 2026/09/28

REPOSITORIES: GEO