Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increased molecular and functional heterogeneity of hematopoietic stem cells contributes to age-related decline of tissue and body function

ABSTRACT: Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Previous studies have demonstrated that aged hematopoietic stem cells (HSCs) are functionally compromised, which at least partly contributes to aging-related decline of the body health. However, the underlying mechanism is largely unknown. Here we reveal a clear aging heterogeneity of old HSCs, which can be marked by the CD150 levels. Comparative molecular and functional analyses revealed that CD150high HSCs have an elder transcriptome, epigenome and diminished repopulation capacity in old mice when compared to CD150low HSCs. Mechanistically, CD150high HSCs from old mice have greatly compromised differentiation capacity compared to that of the CD150low HSCs. Importantly, decreasing the CD150high HSC ratio in old mice can alleviate aging-related functional decline. Thus, our study not only reveals how HSC heterogeneity contributes to aging, but also points to a potential way for rejuvenation.

ORGANISM(S): Mus musculus

PROVIDER: GSE242701 | GEO | 2025/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Increased molecular and functional heterogeneity of hematopoietic stem cells contributes to age-related decline of tissue and body function

Project description:Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Previous studies have demonstrated that aged hematopoietic stem cells (HSCs) are functionally compromised, which at least partly contributes to aging-related decline of the body health. However, the underlying mechanism is largely unknown. Here we reveal a clear heterogeneity of old HSCs, which can be marked by the CD150 levels. Comparative molecular and functional analyses revealed that CD150low HSCs from old mice have a younger aging clock, transcriptome, and better repopulation capacity compared to that of the CD150high HSCs. Mechanistically, CD150high HSCs from old mice have greatly compromised differentiation capacity compared to that of the CD150low HSCs. Importantly, decreasing the CD150high HSC ratio in old mice can alleviate aging-related functional decline. Thus, our study not only reveals how HSC heterogeneity contributes to aging, but also points to a potential way for rejuvenation.

2025-01-02 | GSE233879 | GEO

Transcription profiling of hematopoietic stem cell aging

Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.

2005-08-16 | E-SMDB-3450 | biostudies-arrayexpress

Loss of adrenergic nerves in bone marrow drives hematopoietic stem cell niche aging

Project description:Aging of hematopoietic stem cells (HSCs) is associated with the decline of their regenerative capacity, and multi-lineage differentiation potential, contributing to development of blood disorders. The bone marrow microenvironment was recently suggested to influence HSC aging, however the underlying mechanisms remain largely unknown. Here, we show that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as premature loss of SNS nerves or adrenoreceptor b3 (ADRb3) signaling in the microenvironment accelerated the appearance of HSC aging phenotypes reminiscent of physiological aging. Strikingly, supplementation of ADRb3 sympathomimetics to old mice significantly rejuvenated in vivo function of old HSCs, suggesting that the preservation or restitution of SNS innervation during aging may hold the potential for novel HSC rejuvenation strategies.

2018-05-01 | GSE109546 | GEO

Transcription profiling of long-term hematopoietic stem cells from old and young mice to investigate the mechanisms of hematopoietic aging

2007-12-19 | E-GEOD-4332 | biostudies-arrayexpress

p38α plays differential roles in hematopoietic stem cell activity dependent on aging contexts II

Project description:Hematopoietic stem cells (HSCs) and their progeny sustain lifetime hematopoiesis. Aging alters HSC function, number, and composition and increases risk of hematological malignancies, but how these changes occur in HSCs remains unclear. Signaling via p38MAPK has been proposed as a candidate mechanism underlying induction of HSC aging. Here, using genetic models of both chronological and premature aging, we describe a multimodal role for p38α, the major p38MAPK isozyme in hematopoiesis, in HSC aging. We report that p38α regulates differentiation bias and sustains transplantation capacity of HSCs in the early phase of chronological aging (from young to 1-year-old). However, p38α decreased HSC transplantation capacity in the late progression phase of chronological aging (from 1- to 2-years-old). Furthermore, co-deletion of p38α in mice deficient in Ataxia-telangiectasia mutated (Atm), a model of premature aging, exacerbated aging-related HSC phenotypes seen in Atm single mutant mice. Mechanistically, p38α makes a positive contribution to inflammation during the late phase aging, resulting in defects in 2-year-old HSCs. Overall, we propose multiple functions of p38MAPK, which both promotes and suppresses HSC aging context-dependently.

2021-03-03 | GSE168085 | GEO

p38α plays differential roles in hematopoietic stem cell activity dependent on aging contexts

2021-03-03 | GSE168057 | GEO

Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice

Project description:Increasing evidence links metabolic activity and cell growth to decline in hematopoietic stem cell (HSC) function during aging. The Lin28b/Hmga2 pathway controls tissue development and in the hematopoietic system the postnatal downregulation of this pathway causes a decrease in self renewal of adult HSCs compared to fetal HSCs. Igf2bp2 is an RNA binding protein and a mediator of the Lin28b/Hmga2 pathway, which regulates metabolism and growth signaling by influencing RNA stability and translation of its target genes. It is currently unknown whether Lin28/Hmga2/Igf2bp2 signaling impacts on aging-associated impairments in HSC function and hematopoiesis. Here, we analyzed homozygous Igf2bp2 germline knockout mice and wildtype control animals to address this question. The study shows that Igf2bp2 deletion rescues aging phenotypes of the hematopoietic system, such as the expansion of HSC numbers in bone marrow and the biased increase of myeloid cells in peripheral blood. This rescue of hematopoietic aging coincides with reduced mitochondrial metabolism and glycolysis in Igf2bp2-/- HSCs compared to Igf2bp2+/+ HSCs. Conversely, Igf2bp2 overexpression activates protein synthesis pathways in HSCs and leads to a rapid loss of self renewal by enhancing myeloid skewed differentiation in an mTOR/PI3K-dependent manner. Together, these results show that Igf2bp2 regulates energy metabolism and growth signaling in HSCs and that the activity of this pathways influences self renewal, differentiation, and aging of HSCs.

2024-05-21 | PXD018535 | Pride

Cell size is a determinant of stem cell potential during aging (HSC size-fractionation RNA-seq dataset)

Project description:Stem cells are remarkably small in size. Human hematopoietic stem cells (HSCs) measure a mere 7 μm in diameter. Whether small size is important for stem cell function is unknown. We find that murine HSCs enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. We further show that preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing the size of large HSCs by shortening G1 averts the loss of stem cell potential. Naturally large HSCs also exhibit decreased stem cell potential indicating that large size characterizes exhausted HSCs under physiological conditions. Finally, we show that our findings are relevant to aging. A fraction of murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function and propose that stem cell enlargement contributes to their functional decline during aging.

2021-09-19 | GSE154333 | GEO

Cell size is a determinant of stem cell potential during aging (HSC treatments RNA-seq dataset)

2021-09-19 | GSE154334 | GEO

Genome-wide expression analysis of self renewing hematopoietic stem cells (HSC) in control and CD70TG mice.

Project description:To study the effect of CD27 triggering on HSC biology Ageing of the hematopoietic stem cell (HSC) compartment is characterized by an accumulation of less productive HSCs with impaired lymphoid differentiation capacity, which contributes to age-dependent hematological abnormalities including anemia, myeloproliferative disorders and a decline in adaptive immunity. Since HSCs express the costimulatory receptor CD27 and because inflammation has been associated with HSC ageing, we investigated the effect of stimulation of CD27 by its inflammatory ligand CD70 on HSC maintenance. We found that CD27-triggering during CD70-driven immune activation in young mice enhances HSC self-renewal, leading to accumulation of HSCs to levels comparable with old control mice. These findings indicate that CD27-signaling accelerates HSC ageing, which is supported by the observation that CD27-triggering negatively affects HSC differentiation to the lymphoid lineage and increases myeloid differentiation. This functional change was mirrored by a corresponding difference in gene expression, as microarray analysis indicated that CD27-triggered HSCs have a strongly myeloid-biased gene signature. CD27 signaling also induced enrichment of genes associated with biological processes involved in cellular responses to DNA damage/repair and reactive oxygen species (ROS), which are associated with HSC ageing and related to increased proliferation. Therefore, we postulate that CD27 triggering during chronic inflammation contributes directly to ageing of the hematopoietic compartment.

2014-12-31 | GSE31574 | GEO