Similar Datasets
Project description:The adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging. CD150+CD48-LSK HSCs were double sorted from WT and Lnk-/- mice at both young and old ages (2 months and 20 months, respectively). RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the Penn Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 1.0ST array (Affymetrix).
2012-10-03 | E-GEOD-39553 | biostudies-arrayexpress
Project description:The adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging.
2012-10-03 | GSE39553 | GEO
Project description:Young and Old Pre- and Post-Transplantation ATAC Seq
| PRJNA636794 | ENA
Project description:Ageing of the hematopoietic stem cell (HSC) compartment is characterized by skewing towards the myeloid lineage and reduced stem cell function, the molecular basis of which is largely unknown. Using single cell approaches we identify features contributing to HSC exhaustion with age. A distinct subpopulation of old HSCs carried a signature indicative of impaired stem cell function, activating p53 targets involved in senescence. In the same HSCs, we identified pro-proliferative JAK/STAT and MAPK signalling. We hypothesized that prolonged proliferation of HSCs leads to cell cycle arrest with age and therefore challenged HSCs with a constant proliferative stimulus mediated by a constitutively active form of Jak2, Jak2V617F. Indeed we observed expansion of the p53 positive population and functional impairment of the challenged HSCs. Our results reveal unexpected heterogeneity in the rate of HSC ageing and strongly implicate a role for proliferation in the p53 mediated functional decline of old HSCs.
2017-05-22 | GSE87631 | GEO
Project description:Precise study of HSCs during regeneration has been impeded by the rarity of the HSC population and depletion of phenotypic HSCs early following genotoxic stresses, such as total body irradiation (TBI). We isolated bone marrow (BM) ckit+sca-1+lin- (KSL) cells, which are enriched for HSCs, from adult C57Bl6 mice before and at several time points following TBI, as a means to map the dynamic molecular response of HSC regeneration. We isolated BM KSL cells and myeloid progenitor cells (c-kit+sca-1-lin- cells) at day +14 after irradiation and compared the gene expression profile of regenerating HSCs versus steady state HSCs (non-irradiated) and committed progenitor cells.
2016-04-05 | E-GEOD-79744 | biostudies-arrayexpress
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined1-3, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2020-07-01 | GSE151333 | GEO
Project description:Precise study of HSCs during regeneration has been impeded by the rarity of the HSC population and depletion of phenotypic HSCs early following genotoxic stresses, such as total body irradiation (TBI). We isolated bone marrow (BM) ckit+sca-1+lin- (KSL) cells, which are enriched for HSCs, from adult C57Bl6 mice before and at several time points following TBI, as a means to map the dynamic molecular response of HSC regeneration.
2016-04-05 | GSE79744 | GEO
Project description:Adult and fetal hematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anemia and prenatal death. RISP null fetal HSCs displayed impaired respiration resulting in a decreased NAD+/NADH ratio. RISP null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation concomitant with increases in 2-hydroxyglutarate (2-HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence resulting in severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.
2017-09-13 | PXD006054 | Pride
Project description:Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has been recently reported to impact hematopoiesis. However, there is currently no empirical evidence elucidating the direct impact of gut microbiome on aging hematopoiesis. To assess these potential effects, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed an increment in both the absolute number and the engraftment ability of HSCs. Single cell RNA sequencing depicted overall transcriptional changes of HSCs as well as the bone marrow microenvironment and indicated that gut microbiota from young mice enhanced cell cycle activity of HSCs, attenuated canonical inflammatory signals and mitigated inflammation-associated phenotypes in aging hematopoiesis. Integrated microbiome-metabolome analysis uncovered that FMT reshaped gut microbiota construction and metabolite landscape, while the administration of Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our results highlighted the paramount importance of the gut microbiota in HSC aging and provided a strong rationale to limit hematopoietic exhaustion and treat hematologic disorders.
2023-08-15 | GSE201920 | GEO
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. 3 old mice and 5 young mice were assayed
2007-12-19 | E-GEOD-4332 | biostudies-arrayexpress