Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stem cells: Aging and transcriptional fingerprints.

ABSTRACT: Stem cells are imbued with unique qualities. They have the capacity to propagate themselves through symmetric divisions and to divide asymmetrically to engender new cells that can progress to differentiate into tissue-specific, terminal cell types. Armed with these qualities, stem cells in adult tissues are tasked with replacing decaying cells and regenerating tissue after injury to maintain optimal tissue function. With increasing age, stem cell functional abilities decline, resulting in reduced organ function and delays in tissue repair. Here, we review the effect of aging in five well-studied adult murine stem cell populations and explore age-related declines in stem cell function and their consequences for stem cell self-renewal, tissue homeostasis, and regeneration. Finally, we examine transcriptional changes that have been documented in aged stem cell populations and discuss new questions and future directions that this collection of data has uncovered.

SUBMITTER: Keyes BE

PROVIDER: S-EPMC5748991 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Stem cells: Aging and transcriptional fingerprints.

Keyes Brice E BE Fuchs Elaine E

The Journal of cell biology 20171025 1

Stem cells are imbued with unique qualities. They have the capacity to propagate themselves through symmetric divisions and to divide asymmetrically to engender new cells that can progress to differentiate into tissue-specific, terminal cell types. Armed with these qualities, stem cells in adult tissues are tasked with replacing decaying cells and regenerating tissue after injury to maintain optimal tissue function. With increasing age, stem cell functional abilities decline, resulting in reduce ...[more]

PMID: 29070608

Similar Datasets

Mutational fingerprints of aging.

Project description:Using a lacZ plasmid transgenic mouse model, spectra of spontaneous point mutations were determined in brain, heart, liver, spleen and small intestine in young and old mice. While similar at a young age, the mutation spectra among these organs were significantly different in old age. In brain and heart G:C-->A:T transitions at CpG sites were the predominant mutation, suggesting that oxidative damage is not a major mutagenic event in these tissues. Other base changes, especially those affecting A:T base pairs, positively correlated with increasing proliferative activity of the different tissues. A relatively high percentage of base changes at A:T base pairs and compound mutants were found in both spleen and spontaneous lymphoma, suggesting a possible role of the hypermutation process in splenocytes in carcinogenesis. The similar mutant spectra observed at a young age may reflect a common mutation mechanism for all tissues that could be driven by the rapid cell division that takes place during development. However, the spectra of the young tissues did not resemble that of the most proliferative aged tissue, implying that replicative history per se is not the underlying causal factor of age-related organ-specific differences in mutation spectra. Rather, differences in organ function, possibly in association with replicative history, may explain the divergence in mutation spectra during aging.

| S-EPMC99828 | biostudies-literature

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.

Project description:Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASCs), is increasingly recognized, the study of chronological aging in ASCs is technically difficult and remains poorly understood. Here, we use our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase. Our results reveal novel chronological aging mechanisms in ASCs that are inherently different from differentiated cells and that may reflect an organismal attempt to meet the increased demands of tissue and organ homeostasis during aging. Stem Cells 2017;35:1392-1401.

| S-EPMC5404948 | biostudies-literature

Hematopoietic fingerprints: an expression database of stem cells and their progeny.

Project description:Hematopoietic stem cells (HSCs) continuously regenerate the hematologic system, yet few genes regulating this process have been defined. To identify candidate factors involved in differentiation and self-renewal, we have generated an expression database of hematopoietic stem cells and their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and naive T cells, and B cells. Bioinformatic analysis revealed HSCs were more transcriptionally active than their progeny and shared a common activation mechanism with T cells. Each cell type also displayed unique biases in the regulation of particular genetic pathways, with Wnt signaling particularly enhanced in HSCs. We identified approximately 100-400 genes uniquely expressed in each cell type, termed lineage "fingerprints." In overexpression studies, two of these genes, Zfp 105 from the NK cell lineage, and Ets2 from the monocyte lineage, were able to significantly influence differentiation toward their respective lineages, demonstrating the utility of the fingerprints for identifying genes that regulate differentiation.

| S-EPMC2475548 | biostudies-literature

Organ-, inflammation- and cancer specific transcriptional fingerprints of pancreatic and hepatic stellate cells.

Project description:BACKGROUND: Tissue fibrosis is an integral component of chronic inflammatory (liver and pancreas) diseases and pancreatic cancer. Activated pancreatic- (PSC) and hepatic- (HSC) stellate cells play a key role in fibrogenesis. To identify organ- and disease-specific stellate cell transcriptional fingerprints, we employed genome-wide transcriptional analysis of primary human PSC and HSC isolated from patients with chronic inflammation or cancer. METHODS: Stellate cells were isolated from patients with pancreatic ductal adenocarcinoma (n = 5), chronic pancreatitis (n = 6), liver cirrhosis (n = 5) and liver metastasis of pancreatic ductal adenocarcinoma (n = 6). Genome-wide transcriptional profiles of stellate cells were generated using our 51K human cDNA microarray platform. The identified organ- and disease specific genes were validated by quantitative RT-PCR, immunoblot, ELISA, immunocytochemistry and immunohistochemistry. RESULTS: Expression profiling identified 160 organ- and 89 disease- specific stellate cell transcripts. Collagen type 11a1 (COL11A1) was discovered as a novel PSC specific marker with up to 65-fold higher expression levels in PSC compared to HSC (p < 0.0001). Likewise, the expression of the cytokine CCL2 and the cell adhesion molecule VCAM1 were confined to HSC. PBX1 expression levels tend to be increased in inflammatory- vs. tumor- stellate cells. Intriguingly, tyrosine kinase JAK2 and a member of cell contact-mediated communication CELSR3 were found to be selectively up-regulated in tumor stellate cells. CONCLUSIONS: We identified and validated HSC and PSC specific markers. Moreover, novel target genes of tumor- and inflammation associated stellate cells were discovered. Our data may be instrumental in developing new tailored organ- or disease-specific targeted therapies and stellate cell biomarkers.

| S-EPMC2876060 | biostudies-literature

Rapamycin for aging stem cells.

Project description: Not available

| S-EPMC7467370 | biostudies-literature

Transcriptional analysis of histone deacetylase family members reveal similarities between differentiating and aging spermatogonial stem cells.

Project description:The differentiation of adult stem cells involves extensive chromatin remodeling, mediated in part by the gene products of histone deacetylase (HDAC) family members. While the transcriptional downregulation of HDACs can impede stem cell self-renewal in certain contexts, it may also promote stem cell maintenance under other circumstances. In self-renewing, differentiating, and aging spermatogonial stem cells (SSCs), the gene expression dynamics of HDACs have not yet been characterized. To gain further insight with these studies, we analyzed the transcriptional profiles of six HDAC family members, previously identified to be the most highly expressed in self-renewing SSCs, during stem cell differentiation and aging. Here we discovered that in both differentiating and aging SSCs the expression of Sirt4 increases, while the expression of Hdac2, Hdac6, and Sirt1 decreases. When SSCs are exposed to the lifespan-enhancing drug rapamycin in vivo, the resultant HDAC gene expression patterns are opposite of those seen in the differentiating and aging SSCs, with increased Hdac2, Hdac6, and Sirt1 and decreased Hdac8, Hdac9, and Sirt4. Our findings suggest that HDACs important for stem cell maintenance and oxidative capacity are downregulated as adult stem cells differentiate or age. These results provide important insights into the epigenetic regulation of stem cell differentiation and aging in mammals.

| S-EPMC3605728 | biostudies-literature

Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site.

Project description:Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions.

| S-EPMC3158776 | biostudies-literature

Stem Cells of the Aging Brain.

Project description:The adult central nervous system (CNS) contains resident stem cells within specific niches that maintain a self-renewal and proliferative capacity to generate new neurons, astrocytes, and oligodendrocytes throughout adulthood. Physiological aging is associated with a progressive loss of function and a decline in the self-renewal and regenerative capacities of CNS stem cells. Also, the biggest risk factor for neurodegenerative diseases is age, and current in vivo and in vitro models of neurodegenerative diseases rarely consider this. Therefore, combining both aging research and appropriate interrogation of animal disease models towards the understanding of the disease and age-related stem cell failure is imperative to the discovery of new therapies. This review article will highlight the main intrinsic and extrinsic regulators of neural stem cell (NSC) aging and discuss how these factors impact normal homeostatic functions within the adult brain. We will consider established in vivo animal and in vitro human disease model systems, and then discuss the current and future trajectories of novel senotherapeutics that target aging NSCs to ameliorate brain disease.

| S-EPMC7426063 | biostudies-literature

Effect of aging on stem cells.

Project description:Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.

| S-EPMC5316899 | biostudies-literature

Nfatc1 orchestrates aging in hair follicle stem cells.

Project description:Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbreviated growth phases and are delayed in response to tissue-regenerating cues. Aged HFSCs are poor at initiating proliferation and show diminished self-renewing capacity upon extensive use. Only modestly restored by parabiosis, these features are rooted in elevated cell-intrinsic sensitivity and local elevation in bone morphogenic protein (BMP) signaling. Transcriptional profiling presents differences consistent with defects in aged HFSC activation. Notably, BMP-/calcium-regulated, nuclear factor of activated T-cell c1 (NFATc1) in HFSCs becomes recalcitrant to its normal down-regulating cues, and NFATc1 ChIP-sequencing analyses reveal a marked enrichment of NFATc1 target genes within the age-related signature. Moreover, aged HFSCs display more youthful levels of hair regeneration when BMP and/or NFATc1 are inhibited. These results provide unique insights into how skin SCs age.

| S-EPMC3870727 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data