In vivo partial reprogramming in 4F mice
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ABSTRACT:
PROVIDER: PRJNA787938 | ENA |
REPOSITORIES: ENA
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Project description:Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and cMyc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the lifespan of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, we have performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging in different mouse strains. n=239 tissues from mice. The study involves different conditions (treated and untreated samples) and leads to 7 groups: 1) Black6 mouse +Doxocycline 2) 4 factor mouse+1 month of Doxocycline. 3) 4F mice+7month of Dox 4) 4F+10 months of Dox 5) 4F mice which are relatively old 6) B6 mice that are relatively old 7) 4F mice which are relatively young.
2021-12-10 | GSE190665 | GEO
Project description:Various length of in vivo 4F (four Yamanaka factors) partial reprogramming protocols were performed to evaluate effects of longer-term partial reprogramming in physiologically aging wild-type mice. Here, long-term (7 months) partial reprogramming was induced and transcriptional changes in various tissues were compared to age-matched, untreated mice.
2022-01-11 | GSE190983 | GEO
Project description:Various length of in vivo 4F (four Yamanaka factors) partial reprogramming protocols were performed to evaluate effects of longer-term partial reprogramming in physiologically aging wild-type mice. Here, long-term (10 months) partial reprogramming was induced and transcriptional changes in various tissues were compared to age-matched, untreated mice.
2022-01-11 | GSE190985 | GEO
Project description:Various length of in vivo 4F (four Yamanaka factors) partial reprogramming protocols were performed to evaluate effects of longer-term partial reprogramming in physiologically aging wild-type mice. Here, short-term (1 months) partial reprogramming was induced and transcriptional changes in various tissues were compared to age-matched, untreated mice.
2022-01-11 | GSE190984 | GEO
Project description:In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice
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Project description:Mammalian tissues have a limited regenerative capacity. Previous studies showed that dedifferentiation contributes to tissue regeneration in non-mammalian vertebrate species such as zebrafish and newt. However, dedifferentiation is rarely observed in mammalian tissues even in the neonatal stage and therefore artificial induction of dedifferentiation might enhance regeneration in mammalian tissues. Here we demonstrate that short-term expression of Yamanaka 4 factors (4F) induces dedifferentiation and proliferation in the liver by using lineage-traceable, hepatocyte-specific 4F inducible mouse model. Global transcriptome analysis shows that 4F expression transiently reduces the expression of hepatic-lineage markers and induces the expression of a large set of proliferative markers and epigenetic modifiers along with global epigenetic changes as assessed by DNA-accessibility analysis. More importantly, lineage-tracing experiments showed that 4F-expressing hepatocytes acquire liver stem/progenitor cell markers, suggesting that 4F induces partial reprogramming. Moreover, 4F enhances MyoD-mediated transdifferentiation in the liver, suggesting that 4F endows hepatocytes with plasticity. Lastly, 4F expression attenuated liver injury associated with more proliferative capacity and better survival rate, indicating that 4F enhances liver regeneration. Taken together, these results demonstrate that liver-specific 4F expression induces dedifferentiation and promotes liver regeneration.
2022-04-27 | GSE144600 | GEO
Project description:Partial pluripotent reprogramming has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of partial reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of partial reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that partial reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a partial reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that partial pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.
2022-02-28 | GSE197437 | GEO
Project description:Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems, and warrant further investigation into adapting these approaches for in vivo age reversal.
2024-03-21 | GSE247179 | GEO
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Project description:Partial pluripotent reprogramming in C2C12 myoblasts
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