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Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165996 | GEO | 2023/08/29

REPOSITORIES: GEO

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Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [scRNA-seq]

Project description:Glial progenitor cells (GPCs), the primary source of oligodendrocytes and astrocytes in the human CNS, emerge during the 2nd trimester of human development and subsequently colonize the brain, where a pool remains throughout adulthood. While fetal GPCs are highly migratory and proliferative, there is evidence that their capacities diminish throughout aging or as a result of demyelination-induced exhaustion, thus compromising their ability to mobilize, remyelinate, and self-renew. To investigate this mechanism, we first utilized bulk and scRNA-Sequencing to characterize the human fetal GPC pool and leveraged these data to elucidate transcriptional discrepancies in adult human GPCs. This revealed age-induced transcriptional shifts towards loss of proliferative competency and the potential onset of senescence. Further, we inferred adult networks of direct repressive transcription factor activity that may drive functional decline during GPC aging. Finally, we coupled these data with miRNA profiling of both populations to establish both upstream and parallel arms of repression that may stifle the functional aptitude of aged GPCs. These identified upstream regulators may be ideal therapeutic targets toward rejuvenating GPCs crippled by mitotic exhaustion or aging.

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Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [bulk RNA-seq]

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Human Adult Glial Progenitors Express Distinct miRNA Profiles Compared to their Fetal Counterparts

Project description:Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well as after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent with the repression of genes enabling mitotic expansion, concurrent with the onset of aging-associated transcriptional programs. Adult hGPCs develop a repressive transcription factor network centered on MYC, and regulated by ZNF274, MAX, IKZF3, and E2F6. Individual over-expression of these factors in iPSC-derived hGPCs lead to a loss of proliferative gene expression and an induction of mitotic senescence, replicating the transcriptional changes incurred during glial aging. miRNA profiling identifies the appearance of an adult-selective miRNA signature, imposing further constraints on the expansion competence of aged GPCs. hGPC aging is thus associated with acquisition of a MYC-repressive environment, suggesting that suppression of these repressors of glial expansion may permit the rejuvenation of aged hGPCs.

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Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [scRNA-seq]

Project description:Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [scRNA-seq]

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Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [bulk RNA-seq]

Project description:Human Adult Glial Progenitors Are Transcriptionally Distinct from Their Fetal Counterparts [bulk RNA-seq]

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