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| Status |
Public on Feb 12, 2024 |
| Title |
Human Adult Glial Progenitors Express Distinct miRNA Profiles Compared to their Fetal Counterparts |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
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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| Overall design |
Adult (A2B5+; n=4) and fetal (CD140a+; n=4) hGPC cell suspensions were isolated via MACS as noted above, and their miRNA isolated using miRNeasy kits according to manufacturer instructions (QIAGEN). Purified miRNA was then prepared and profiled on Affymetrix GeneChip miRNA 3.0 Arrays as instructed by their standard protocol. Raw CEL files were then read into R via the oligo package and samples were normalized via robust multi-array averaging (RMA). Probes were then filtered for only human miRNAs according to Affymetrix's annotation, and differential expression was carried out in limma where significance was established at an adjusted p-value < 0.01.
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| Contributor(s) |
Goldman SA, Mariani JN, Chandler-Militello D |
| Citation(s) |
38719882 |
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| Submission date |
Feb 12, 2024 |
| Last update date |
May 13, 2024 |
| Contact name |
Steven Goldman |
| Organization name |
University of Rochester Medical Center
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| Department |
Center for Translational Neuromedicine
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| Lab |
Goldman Lab
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| Street address |
601 Elmwood Ave
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| City |
Rochester |
| State/province |
NY |
| ZIP/Postal code |
14642 |
| Country |
USA |
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| Platforms (1) |
| GPL16384 |
[miRNA-3] Affymetrix Multispecies miRNA-3 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1075680 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255589_RAW.tar |
27.5 Mb |
(http)(custom) |
TAR (of CEL) |
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