Non-monotonic changes in Progenitor Cell Behavior and Gene expression during aging of the Adult Neural Stem Cell Niche
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA413400 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6133390.fastq.gz | Fastqsanger.gz | |||
| SRR6133391.fastq.gz | Fastqsanger.gz | |||
| SRR6133392.fastq.gz | Fastqsanger.gz | |||
| SRR6133393.fastq.gz | Fastqsanger.gz | |||
| SRR6133384.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18 and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1+ progenitor cells decrease in number and proliferation between 2-18 months, but these increased between 18-22 months. Time-lapse lineage analysis of 944 V-SVZ cells showed that age-related declines in neurogenesis were recapitulated in vitro in clones. However, activated type B/type C cell clones divide slower from 2-18 months, then unexpectedly faster at 22 months, with impaired transition to type A neuroblasts. Our findings indicate that aging of the V-SVZ involves significant non-monotonic changes that are programed within progenitor cells, and observable independent of the aging niche.
2017-11-16 | GSE104651 | GEO
Project description:During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we used quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generated a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we revealed signaling via Integrins, Lrp1, Egfr and Cd44 as the major cell communication axes perturbed through aging. We investigated the effect of Smoc2, a secreted protein that accumulates with aging, originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Itgb1/MAPK signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.
2021-11-10 | PXD023628 | Pride
Project description:During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we used quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generated a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we revealed signaling via Integrins, Lrp1, Egfr and Cd44 as the major cell communication axes perturbed through aging. We investigated the effect of Smoc2, a secreted protein that accumulates with aging, originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Itgb1/MAPK signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.
2021-11-10 | PXD023643 | Pride
Project description:Adult stem cells support tissue homeostasis and repair throughout the life of an individual. However, numerous intrinsic and extrinsic changes occur with age that result in altered stem cell behavior and reduced tissue maintenance and regeneration. In the Drosophila testis, stem cells surround and contact the apical hub, a cluster of somatic cells that express the self-renewal factor Unpaired (Upd), which activates the JAK-STAT pathway in adjacent stem cells. However, aging results in a dramatic decrease in upd expression, with a concomitant loss of germline stem cells (GSCs). Here we present genetic and biochemical data to demonstrate that IGF-II mRNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd RNA and contribute to maintenance of the niche. However, Imp expression decreases in hub cells of older males, similar to upd, which is due to targeting of Imp by the heterochronic microRNA let-7. Therefore, in the absence of Imp, upd mRNA becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for aging-related changes in stem cell behavior will lead to the development of strategies to treat age-onset diseases and facilitate stem cell based therapies in older individuals. Examination of small RNA levels in testes from young (1day old) and aged (30days old) males of Drosophila melanogaster by deep sequencing (using Illumina GAII).
2012-05-31 | E-GEOD-37041 | biostudies-arrayexpress
Project description:Niche stiffness underlies the aging of CNS progenitor cells.
| PRJNA552875 | ENA
Project description:Hematopoietic aging is defined by a loss of regenerative capacity and skewed differentiation from hematopoietic stem cells (HSC) leading to dysfunctional blood production. Signals from the bone marrow (BM) microenvironment dynamically tailor hematopoiesis, but the effect of aging on the niche and the contribution of the aging niche to blood aging still remains unclear. Here, we show the development of an inflammatory milieu in the aged marrow cavity, which drives both niche and hematopoietic system remodeling. We find decreased numbers and functionality of osteogenic endosteal mesenchymal stromal cells (MSC), expansion of pro-inflammatory perisinusoidal MSCs, and deterioration of the central marrow sinusoidal endothelium, which together create a self-reinforcing inflamed BM milieu. Single cell molecular mapping of old niche cells further confirms disruption of cell identities and enrichment of inflammatory response genes. Inflammation, in turn, drives chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors, which promotes myeloid differentiation at the expense of lymphoid and erythroid commitment, and hinders hematopoietic regeneration. Remarkably, both defective hematopoietic regeneration, niche deterioration and HSC aging can be improved by blocking inflammatory IL-1 signaling. Our results indicate that targeting the pro-inflammatory niche milieu can be instrumental in restoring blood production during aging.
2022-11-02 | GSE168613 | GEO
Project description:Adult stem cells support tissue homeostasis and repair throughout the life of an individual. However, numerous intrinsic and extrinsic changes occur with age that result in altered stem cell behavior and reduced tissue maintenance and regeneration. In the Drosophila testis, stem cells surround and contact the apical hub, a cluster of somatic cells that express the self-renewal factor Unpaired (Upd), which activates the JAK-STAT pathway in adjacent stem cells. However, aging results in a dramatic decrease in upd expression, with a concomitant loss of germline stem cells (GSCs). Here we present genetic and biochemical data to demonstrate that IGF-II mRNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd RNA and contribute to maintenance of the niche. However, Imp expression decreases in hub cells of older males, similar to upd, which is due to targeting of Imp by the heterochronic microRNA let-7. Therefore, in the absence of Imp, upd mRNA becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for aging-related changes in stem cell behavior will lead to the development of strategies to treat age-onset diseases and facilitate stem cell based therapies in older individuals.
2012-05-31 | GSE37041 | GEO
Project description:Fibroblasts residing in the connective tissue of all organs constitute the stem cell niche particularly in connective tissue rich organs like skin. Though the impact of the connective tissue resident fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. Here, we report a novel mechanism of redox-dependent activation of the transcription factor JunB, which through concomitant upregulation of cyclin dependent kinase inhibitor p16INK4A and repression of IGF-1 dependent cell growth and protein translation initiates the installment of irreversible fibroblast senescence. Fibroblast senescence in turn profoundly disrupts the metabolic and structural niche and its essential interactions with different stem cells thus enforcing depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast niche-specific knock out mouse - by the reinstatement of IGF-1 and p16 levels - fully restored skin stem cell pools and overall tissue integrity of the skin. We here uncovered a previously unreported role of JunB in the control of the endogenous connective tissue niche and identified promising targets to combat skin aging and associated pathologies.
2021-07-16 | GSE180008 | GEO
Project description:Tissue homeostasis and regeneration require activation and subsequent lineage commitment of tissue-resident stem cells (SCs). These state changes are controlled by epigenetic barriers. Using hair follicle stem cells (HFSCs) as paradigm, we studied how aging impacts the chromatin landscape and function of mammalian SCs. Analyses of genome-wide chromatin accessibility revealed that aged HFSCs displayed widespread reduction of chromatin accessibility specifically at key SC self-renewal and differentiation genes that were characterized by bivalent promoters carrying both activating and repressive chromatin marks. Consistently, aged HFSCs showed reduced self-renewing capacity and attenuated ability to activate expression of these bivalent genes upon regeneration. These functional defects were niche-dependent as transplantation of aged HFSCs into young recipients or into ex vivo niches restored SC functions and transcription of poised genes. Mechanistically, aged HFSC niche displayed wide-spread alterations in extracellular matrix composition and mechanics, resulting in compressive forces on SCs and subsequent transcriptional repression, leading to loss of bivalent promoters. Tuning tissue mechanics both in vivo and in vitro recapitulated age-related SC changes, implicating niche mechanics as a central regulator of genome organization and function leading to age-dependent SC exhaustion.
2021-05-07 | PXD018352 | Pride
Project description:Loss of adrenergic nerves in bone marrow drives hematopoietic stem cell niche aging
| PRJNA431366 | ENA