A comprehensive transcriptome signature of murine hematopoietic stem cell aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE166674 | GEO | 2021/04/02
REPOSITORIES: GEO
Similar Datasets
Project description:We have performed RNA-seq in highly purified Hematopoeitic Stem cells (HSC, LSK/SLAM) from young (4-5mo) and old (20-24mo) C57BL/6J in order to investigate differences in gene expression between these groups.
2020-10-20 | GSE128050 | GEO
Project description:In BRE-GFP transgenic mice BMP activated cells are marked by GFP expression. Analysis of GFP+ and GFP- LSK-SLAM HSC enriched fractions from fetal liver and adult bone marrow shows the interinsic differences in the genetic program of these two HSC enriched fractions. RNAseq of GFP+ and GFP- LSK-SLAM cells from BRE-GFP transgenic mice Fetal liver and adult bone marrow
2015-06-23 | E-GEOD-70132 | biostudies-arrayexpress
Project description:In BRE-GFP transgenic mice BMP activated cells are marked by GFP expression. Analysis of GFP+ and GFP- LSK-SLAM HSC enriched fractions from fetal liver and adult bone marrow shows the interinsic differences in the genetic program of these two HSC enriched fractions.
2015-06-23 | GSE70132 | GEO
Project description:To begin to explore mechanisms by which microbiota signals regulate HSC lineage bias, gene expression profiling was performed on sorted LSK-SLAM cells from aged SPF and aged GF mice.
2021-11-10 | GSE183138 | GEO
Project description:Here, we present a Small RNA-Seq dataset of isolated mouse hematopoietic stem cells (HSC LSK slam; Lineage- Sca-1+ c-Kit+ CD150+CD48-) of Meg3 KO (induced MxCre Meg3mat flox/pat wt) and control (induced MxCre) cells
2019-02-15 | E-MTAB-7519 | biostudies-arrayexpress
Project description:Here we tracked transcriptional changes in LT, ST-HSC and MLP after transplantation into immunocompromised mice. We show that LT- and ST-HSC activate similar pathways upon transplantation but they modulate distinct sets of genes. Total RNA was obtained from flow-sorted populations of human LT-, ST-HSC and MLP isolated from cord blood or immunocompromised mice transplanted with human at hematopoeitic progenitors at different time points after transplantation.
2015-02-20 | E-GEOD-58299 | biostudies-arrayexpress
Project description:The infant leukemia-associated gene, Ott1 (Rbm15), has broad regulatory effects on embryonic development and hematopoiesis. Embryonic deletion of Ott1 results in defects to the placenta, spleen and heart. Conditional deletion within the adult hematopoietic compartment demonstrates a requirement in pre-B development and inhibitory roles in myeloid progenitor and megakaryocyte populations. Ott1-deleted bone marrow has an expansion of the Lin- Sca-1+ c-Kit+ (LSK) population which includes the hematopoietic stem cell (HSC) population. Functional HSC testing through competitive repopulation of irradiated recipients demonstrated however, a severe defect in Ott1-deficient HSCs, despite adequate numbers of immunophenotypically identified long term HSCs. Although mice deleted in situ for Ott1 are able to maintain hematopoiesis in steady state over a normal lifetime, but when subjected to proliferative stress, the HSC population loses the self-renewing, G0 fraction and undergoes bone marrow failure. Therefore, Ott1 is required for maintaining HSC quiescence during proliferative stress. To investigate the downstream effects of Ott1 loss, LSK cells were sorted from Ott1-deleted mice and controls then global gene expression profiles were generated through hybridization of total RNA onto microarrays. Gene set enrichment analysis showed significant enrichment with genes altered in aged HSCs. Ott1-deficient HSCs were found to have other aging-associated features such as increased DNA damage, NF kappa B activation and p38Mapk activation, suggesting Ott1 controls pathways also involved in the aging process. Six week old Ott1 flox/null Tg-Mx1cre mice and littermate controls possessing a wild type Ott1 allele were injected with 250 mcg intraperitoneal pIpC every other day for 3 doses. Six weeks post-pIpC, bone marrow was harvested, labeled with lineage markers (B220, CD19, CD4, CD8, CD3, IL7R, Terr119 and Gr-1) and depleted using magnetic beads. The remaining cells were labeled for c-Kit and Sca-1 and the Lin- Sca-1+ c-Kit+ (LSK) population was sorted using a FACSAria cell sorter (BD Biosciences). Approximately 10,000 LSK cells per mouse were isolated from 3 Ott1 flox/null Tg-Mx1cre mice and 3 controls. RNA was extracted using the RNeasy Micro kit (Qiagen, Valencia, CA) and treated with RNAse-free DNAse (Qiagen, Valencia, CA). 50 ng of purified total RNA was linearly amplified using the Ovation RNA amplification system V2 (Nugen, San Carlos, CA) and biotinylated with the FL-Ovation Biotin Module V2 (Nugen, San Carlos, CA) per the supplied protocol. cDNA was then hybridized to Affymetrix Mouse expression array 430A2.0 chips by the Dana Farber Microarray Core Facility (Boston, MA). The raw gene expression values were preprocessed with robust multi-array analysis (RMA) algorithm using BioConductor software.
2012-04-23 | E-GEOD-37047 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+,Sca1+) progenitors after in vivo pharmacological perturbation of niche signals interferon, granulocyte-colony stimulating factor (G-CSF), and prostaglandin. We identified six HSC states that are characterized by enrichment but not exclusive expression of marker genes. External signals induced rapid transitions between HSC states but transcriptional response varied both between external stimulants and within the HSC population for a given perturbation. In contrast to LSK progenitors, HSCs were characterized by a greater link between molecular signatures at baseline and in response to external stressors. Chromatin analysis of unperturbed HSCs and LSKs by scATAC-Seq suggested some HSC-specific, cell intrinsic predispositions to niche signals. We compiled a comprehensive resource of HSC- and LSK progenitor-specific chromatin and transcriptional features that represent determinants of signal receptiveness and regenerative potential during stress hematopoiesis.
2021-12-22 | GSE165844 | GEO
Project description:Little is known of hematopoietic stem (HSC) and progenitor (HPC) cell self-renewal. The role of Brahma (BRM), a chromatin remodeler, in HSC/HPC function is unknown. Bone marrow (BM) from Brm-/- mice manifested increased numbers of long- and short-term HSCs, GMPs, and increased numbers and cycling of functional HPCs. Brm-/- HSC/HPC show demonstrated functional differences compared to wildtype HSC/HPC in vivo and ex vivo, due in part to increased intracellular valine in lineage negative BM. To determine changes in gene programs associated with loss of BRM, we performed RNA sequencing on Brm-/- LSK cells. Brm-/- LSK exhibited upregulated interferon response/cell cycle gene programs, suggesting important extrinsic effects on primitive HSC/HPC from more mature HPC due to the absence of BRM.
2021-11-08 | GSE183430 | GEO
Project description:Ubiquitination is a post-translational mechanism of control of diverse cellular processes. We focus here on the ubiquitin ligase Fbw7, a recently identified hematopoietic tumor suppressor that can target for degradation several important oncogenes including Notch1, c-Myc and cyclin E. We have generated conditional Fbw7 knock-out animals and inactivated the gene in hematopoietic stem cells (HSC) and their differentiated progeny. Deletion of Fbw7 specifically and rapidly affects the HSC compartment in a cell-autonomous manner. Fbw7-/- HSCs show defective maintenance of quiescence, leading to impaired self-renewal and a severe loss of competitive repopulating capacity. Furthermore, Fbw7-/- HSC are unable to colonize the thymus leading to a profound depletion of T cell progenitors. Deletion of Fbw7 in bone marrow stem cells and progenitors leads to the stabilization of c-Myc, a transcription factor previously implicated in HSC self-renewal. On the other hand, neither Notch1 nor cyclin E are stabilized in the bone marrow of Fbw7 deficient mice. Genome-wide transcriptome studies of Fbw7-/- HSC and hematopoietic progenitors indicate that Fbw7 controls, through the regulation of HSC cell cycle entry, the global transcriptional âsignatureâ that is associated with the quiescent, self-renewing HSC phenotype. Transcriptional consequences of inactivating Fbw7 in LKS cells. Experiment Overall Design: Four samples were analyzed: wild-type (WT) control and Fbw7-deficient (FBW7) Lin-ckit+Sca1+ (LSK) cells, as well as Lin-ckit+Sca1- myeloid progenitor (MP) cells, which served as a control for LSK-enriched/specific genes. Total bone marrow cells were pooled from three WT and three FBW7 mice before sorting LSK and MP populations.
2008-06-11 | E-GEOD-11178 | biostudies-arrayexpress