Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNAseq data from Dlk1+ and Dlk1- aged murine hematopoietic stem cells

ABSTRACT: Quantification of gene expression noise on young versus aged bone marrow HSCs at single-cell resolution revealed Dlk1 increases both noise and expression levels upon aging. Dlk1, encoding a cell surface non-canonical Notch ligand, is partially expressed in the LT-HSC compartment, without generating clusters of individual subpopulations by conventional clustering analysis. We aimed to characterize the trascriptome of aged LT-HSC with positive and negative expression of Dlk1 cells. Dataset created as part of the publication: "VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells"

ORGANISM(S): Mus musculus

PROVIDER: GSE185637 | GEO | 2023/05/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell RNAseq data from Dlk1+ and Dlk1- aged murine hematopoietic stem cells

Project description:Single cell RNAseq data from Dlk1+ and Dlk1- aged murine hematopoietic stem cells

| PRJNA770249 | ENA

LT-HSC from young (2mo), middle-age (12mo) and old (22mo) mice for RNA-seq

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

LT-HSC from young and middle-age mice stimulated with IGF1 RNA-seq

2020-02-08 | GSE144934 | GEO

LT-HSC from middle-age mice stimulated with IGF1 ATAC-seq

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 defined, 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.

2021-01-12 | GSE164609 | GEO

LT-HSC re-isolated from tranplants altering the age (young and middle age) of the donor LT-HSC, support cells and recipient mice

2020-02-08 | GSE144933 | GEO

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma

Project description:Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, the often fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma. Plasma membrane-enriched mass spectrometry identified 1,461 cell surface proteins in cell lines and 1,401 in xenograft models, respectively. Additional proteogenomic analyses revealed 71 high-confidence candidate immunotherapeutic targets and we prioritized Delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlated with the presence of a super-enhancer spanning the DLK1 locus. Robust cell surface expression of DLK1 was validated by immunofluorescence, flow cytometry, and immunohistochemistry. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells resulted in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), showed potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Finally, we also found that DLK1 is highly expressed in several adult cancer types including adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PCPG) and small cell lung cancer (SCLC) suggesting potential clinical benefit beyond neuroblastoma. A clinical trial has been developed for evaluating ADCT-701 in neuroendocrine tumors in adults (https://www.clinicaltrials.gov/study/NCT06041516?term=adct-701&rank=1). Therefore, comprehensive characterization of cancer surfaceomes can provide biologically relevant immunotherapy targeting strategies.

2024-10-23 | PXD047474 | Pride

Methylomic analysis identifies the involvement of migration and adhesion genes in the ageing of primary haematopoietic stem cells

Project description:we utilize Nano-MeDIP-seq for the analysis of the LT-HSC methylome and, for the first time, simultaneously interrogate the methylome and transcriptome of a homogeneous population of primary murine HSCs, in order to define the underlying causes of changes in HSC functionality during normal ageing. We isolated and phenotyped primary LT-HSCs from young, middle-aged and old mice and subjected them to comprehensive methylome (MeDIP-seq) and transcriptome (RNA-seq) analysis.

2013-11-01 | E-GEOD-41658 | biostudies-arrayexpress

Loss of Phf6 prevents aging associated transcriptomic profile changes in LT-HSCs

Project description:Loss of Phf6 prevents the functional decline and immunophenotypic changes associated with age-related, long-term repopulating hematopoietic stem cell (LT-HSC) exhaustion. To identify the underlying molecular mechanisms that account for these differences, we performed RNA-seq profiling of LT-HSCs isolated from the bone marrow of Phf6 wild-type and knock-out, young (16-week-old) and aged (24-month-old) C57BL/6 mice. Our analysis revealed that LT-HSCs isolated from 24-month-old, Phf6 knockout mice retained the molecular signatures associated with young LT-HSCs whereas LT-HSCs isolated from aged, Phf6 wild-type mice acquired signatures consistent with HSC exhaustion. Mechanistically, these data revealed important roles for key metabolic pathways including glutathione metabolism and sterol biosynthesis, as well as cell-cell interaction and signaling pathways such as the interferon and TGF-beta responses.

2022-11-01 | GSE165695 | GEO

Transcription profiling of human control (hMSC-TERT) vs Dlk overexpressing cells (hMSC-Dlk1) to analyse Dlk1-mediated signaling pathways during hMSC differentiation

Project description:We aimed in this study to identify the differentially regulated genes by Dlk1 in hMSC cells using microarray technology in order to gain a better understanding of Dlk1-mediated signaling pathways during hMSC differentiation. Both control (hMSC-TERT)(not expressing Dlk1) and Dlk1 overexpressing cells (hMSC-Dlk1) were cultured in triplicate at 3×104 cells/cm2 in Petri-dish in standard growth medium. At 90-100% confluence, highly purified total cellular RNA was isolated from each of three independent cultures per cell line using RNeasy Kit (QIAGEN Nordic, West Sussex, UK) according to the manufacturer?s instructions

2006-02-10 | E-MEXP-560 | biostudies-arrayexpress

Small Nucleolar RNAs in the Dlk1-Gtl2 Imprinting Locus Maintains LT-HSC Self-renewal by Regulation of rRNA Modification and Translation

Project description:Small Nucleolar RNAs in the Dlk1-Gtl2 Imprinting Locus Maintains LT-HSC Self-renewal by Regulation of rRNA Modification and Translation

| PRJNA701172 | ENA

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