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Impact of partial reprogramming, aging, and differentiation on primary neural stem cells

ABSTRACT: Partial reprogramming is of interest as a potential strategy to improve or erase aging hallmarks. The mechanisms underlying its effect on specific cell types remain unknown. Here, we investigate early transcriptional changes that could mediate the effects of reprogramming on old neural stem cells (NSCs) and their differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE245385 | GEO | 2024/02/04

REPOSITORIES: GEO

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In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice (10 months; long-term treatment)

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

In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice (1 months; sort-term treatment)

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

In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice (7 months; long-term treatment)

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

Partial pluripotent reprogramming in C2C12 myoblasts

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

Pluripotent Stem Cells Induced from Mouse Neural Stem Cells and Small Intestinal Epithelial Cells by Small Molecule Compounds

Project description:Pluripotent stem cells can be generated by pure small molecule compounds. However, only fibroblasts, a heterogeneous cell population, were reported for use in chemical reprogramming, and the efficiency is relatively low, raising the possibility that chemically induced pluripotent stem cells (CiPSCs) are derived from a specific cell subpopulation residing in fibroblast culture. Thus, it is of interest to know whether chemical reprogramming can be induced in other cell types, even using the same chemical cocktail. Here, using lineage tracing, we verify the generation of CiPSCs from fibroblasts. We further demonstrate that neural stem cells (NSCs) and small intestinal epithelial cells (IECs), cell types from the ectoderm and endoderm, respectively, can be chemically reprogrammed into pluripotent stem cells. CiPSCs derived from NSCs and IECs resemble mouse embryonic stem cells (ESCs) in terms of proliferation rate, global gene expression profiling, epigenetic status, self-renewal and differentiation capacity, and germline transmission competency. Interestingly, in the chemical reprogramming process from different cell types, a pluripotency gene Sall4 was commonly expressed in the initial stage, and the same core small molecules were required, suggesting conservatism underlying chemical reprogramming from different cell types. Moreover, the use of these small molecules should be fine-tuned to meet the requirement of reprogramming from different cell types. Together, these findings demonstrate that our reported chemical reprogramming approach can be reproduced in different cell types and suggest that chemical reprogramming is a promising strategy with the potential to be extended to more initial cell types. We analyzed the gene expression profiles of NSC-derived CiPSCs and IEC-derived CiPSCs ,using RNA-Sequencing. NSCs, IECs, and embryonic stem cells (R1) are controls.

2016-07-03 | E-GEOD-75522 | biostudies-arrayexpress

Partial pluripotent reprogramming in C2C12 myoblasts

Project description:Partial pluripotent reprogramming in C2C12 myoblasts

| PRJNA810342 | ENA

In vivo partial reprogramming in 4F mice

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

In vivo partial reprogramming in 4F mice

Project description:In vivo partial reprogramming in 4F mice

| PRJNA787938 | ENA

Early Stem Cell Aging in the Mature Brain

Project description:Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell behavior represent early targets to enhance stem cell function later in life. Here, we pinpoint multiple factors that disrupt neural stem cell (NSC) behavior in the adult hippocampus. Clonal tracing showed that NSCs exhibit asynchronous depletion by identifying short-term (ST-NSC) and long-term NSCs (LT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent LT-NSCs are maintained for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of molecular aging in the mature brain and identified tyrosine-protein kinase Abl1 as an NSC pro-aging factor. Treatment with the Abl-inhibitor Imatinib increased NSC proliferation without impairing NSC maintenance in the middle-aged brain. Our study indicates that hippocampal NSCs are particularly vulnerable to cellular aging, yet NSC function can be partially restored.

2021-03-03 | GSE168031 | GEO

Oct4-Induced Pluripotency in Adult Neural Stem Cells

Project description:The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.

2009-02-01 | GSE12499 | GEO

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