Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons.
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ABSTRACT:
SUBMITTER: Moroz LL
PROVIDER: S-EPMC2910937 | biostudies-literature | 2010
REPOSITORIES: biostudies-literature
Publications
Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons.
Moroz Leonid L LL Kohn Andrea B AB
Frontiers in aging neuroscience 20100519
Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between youn ...[more]
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Project description:ObjectiveThe cholinergic deficit is thought to underlie progressed cognitive decline in Alzheimer Disease. The lineage reprogramming of somatic cells into cholinergic neurons may provide strategies toward cell-based therapy of neurodegenerative diseases.Methods and resultsHere, we found that a combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2, Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular pericytes (HBVPs) into cholinergic neuronal cells. Intriguingly, the inducible effect screening of reprogramming factors showed that a single reprogramming factor, Myt1l, induced cells to exhibit similarly positive staining for Tuj1, MAP2, ChAT, and VAChT upon lentivirus infection with the 5Fs after 30 days. HBVP-converted neurons were rarely labeled even after long-term incubation with BrdU staining, suggesting that induced neurons were directly converted from HBVPs rather than passing through a proliferative state. In addition, the overexpression of Myt1l induced the elevation of Ascl1, Brn2, and Ngn2 levels that contributed to reprogramming.ConclusionsOur findings provided proof of the principle that cholinergic neurons could be produced from HBVPs by reprogramming factor-mediated fate instruction. Myt1l was a critical mediator of induced neuron cell reprogramming. HBVPs represent another excellent alternative cell resource for cell-based therapy to treat neurodegenerative disease.
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