Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells

ABSTRACT: Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of Ltbr-deficient and -proficient LT/ST-HSCs isolated from chimeric mice. Methods: Transcriptomic profiles of Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice 6 weeks after reconstitution were assessed in triplicate by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 60 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice. RNA-seq. data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the Ltbr-/- and Ly5.1 LT/ST-HSCs were identified with a fold change ≥1.5 and FDR p-value <0.05. Conclusions: Our study represents the first detailed transcriptome analysis of Ltbr-deficient and -proficient LT/ST-HSCs, with biologic replicates, generated by RNA-seq. technology. Our results show that Ltbr signaling regulates HSC proliferation and differentiation. Evaluation of mRNA content in Ltbr-/- LT/ST-HSCs revealed that Ltbr-deficiency enhances HSC proliferation, differentiation, cell cycle and reduces the activity of canonical NFkB signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE141206 | GEO | 2020/10/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profiling of LT-HSCs and ST-HSCs conditionally expressing MLL-ENL

Project description:We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis. For initial screening of candidate genes invloved in the leukemic transformation, total RNA was extracted from colony-forming cells derived from LT-HSCs and ST-HSCs transduced with CreER or mock. Four samples were analyzed, and CreER-transduced LT/ST-HSC-derived cells were compared with mock-transduced LT/ST-HSC-derived cells, while CreER/mock-transduced LT-HSC-derived cells were compared with CreER/mock-transduced ST-HSC-derived cells.

2013-07-17 | E-GEOD-48539 | biostudies-arrayexpress

Expression data of freshly isolated and sorted HSC populations from murine fetal liver or adult bone marrow [array]

Project description:We isolated murine fetal liver and murine adult bone marrow and FACS sorted LT-HSCs, ST-HSCs and MPPs. We used global expression analysis by microarray to compare regulated genesets in different HSC populations in fetal and adult.

2023-04-30 | GSE173158 | GEO

Chromatin remodeling and dynamics of hematopoietic stem cells and progenitors

Project description:Hematopoietic stem cells (HSCs) have the capability to self-renew and differentiate into all blood cell lineages. How chromatin state regulates self-renewal and differentiation of HSC is not fully understood. Here, we provided the first global landscape of chromatin state in long term (LT)-HSCs, short term (ST)-HSCs and multipotent progenitor (MPP) by ATAC-seq analysis. We discovered that the promoter regions of genes that control cell cycle, and several important miRNAs were maintained as open chromatin state in HSCs. In addition, we found that promoter-TSS regions of many genes were occupied by nucleosomes in LT/ST-HSC and they become open chromatin regions in MPP. Furthermore, we uncovered 166 known transcription factors (TFs) including C/EBPs, GABPA, and FLI1can access to the promoter open chromatin in HSCs, and quarter of them displayed cell type-specific manner. Among them, we identified DNA cis-element of Krüppel-like factor family (KLF9, KLF10 and KLF14) were specifically enriched in LT-HSC. Meanwhile, we found that 8299 enhancers are established concomitantly with the formation of open chromatin sites, and they can be accessed by 153 TFs including GABPA, CTCF and RNUX1/RUNX2. Near hundred TF-binding motif are enriched in both promoter and enhancers, indicating they may direct the interaction between promoters and enhancers. Finally, we found 21.7% poised enhancers were preset in LT/ST-HSCs, and became active enhancers in MPP. Together, our finding provides new insightinto how chromatin state and transcriptionalregulatory networkare remodeledin promoter and enhancer regions during the differentiation of LT/ST-HSC to MPP.

2017-06-05 | GSE84959 | GEO

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

Project description:Small nucleolar RNA (snoRNA) are non-coding RNAs, which participate in the cleavage and chemical modification of ribosomal RNAs (rRNAs) and small nuclear RNAs. However, the roles of snoRNA in homeostasis of hematopoietic stem cells(HSCs) have not been studied. We isolated four hematopoietic stem and progenitor cells (HSPCs) (LT-HSCs, IT-HSCs, ST-HSCs, and MPPs) from the bone marrow (BM) of C57BL/6 mice and performed small RNA-seq. We found SnoRNAs belonging to SNORD113-114 cluster were specifically enriched in LT-HSCs, and their expression decreased dramatically with HSC differentiation. To explore function of snoRNAs in SNORD113-114 cluster in HSCs, we established maternally KO mice by CRISPR-Cas9 technology. Here, we used scRNA-seq to examine HSC RNA profiles influenced by SNORD113-114 cluster KO.

2024-06-03 | GSE166516 | GEO

RNA-sequencing analysis of murine Hematopoietic Stem Cells treated with Nicotinamide Riboside

Project description:LT-HSC and ST-HSCs were FACS sorted (>10^4cells per sample), cultured for two days in presence or absence of 1 mM NR and total RNA extracted

2019-01-17 | GSE125211 | GEO

Effect of bioengineered niches on perivascular stem cell phenotype.

Project description:Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via allogeneic stem cell transplantation (alloSCT), to engraft and repopulate the blood system. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs (ST-HSC) and progenitor populations at the expense of naïve LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs or pericytes). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1 expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1 expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

2024-04-25 | GSE265789 | GEO

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

Project description:Small nucleolar RNA (snoRNA) are non-coding RNAs, which participate in the chemical modification of ribosomal RNAs (rRNAs) and small nuclear RNAs. However, the roles of snoRNA in homeostasis of hematopoietic stem cells(HSCs) have not been studied. We isolated four hematopoietic stem and progenitor cells (HSPCs) (LT-HSCs, IT-HSCs, ST-HSCs, and MPPs) from the bone marrow (BM) of C57BL/6 mice and performed small RNA-seq. We found SnoRNAs belonging to SNORD113-114 cluster were specifically enriched in LT-HSCs, and their expression decreased dramatically with HSC differentiation. Here, we used a modified small RNA-seq method to examine snoRNA profiles of hematopoietic progenitor and mature cells in WT mice.

2024-10-30 | GSE269874 | GEO

Transcription profiling of mouse normal LT-HSC vs ST-HSC

Project description:Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. Experiment Overall Design: LT-HSC (Lin-cKit+Sca1+CD34-CD135-) and ST-HSC (Lin-cKit+Sca1+CD34+CD135-) cells were prospectively sorted from the BM of MxCre-.Pbx1f/f control mice harvested 4 weeks after the last injection of poly(I:C).

2008-06-20 | E-GEOD-9189 | biostudies-arrayexpress

Single cell hibernation cultures identify molecules dispensable for haematopoietic stem cell self-renewal

Project description:Advances in the isolation and gene expression profiling of single haematopoietic stem cells (HSCs) have permitted in-depth resolution of their molecular program. However, long-term HSCs (LT-HSCs) can only be isolated to near purity from adult mouse bone marrow, thereby precluding studies of their molecular program in different physiological states. Here, we describe a powerful 7-day culture system that removes single LT-HSCs from their native bone marrow microenvironment without compromising their functional potential. LT-HSCs are maintained as single cells and retain full HSC function compared to freshly isolated LT-HSCs with respect to divisional kinetics, colony forming cell potential (73.9%), and transplantation into primary (53%) and secondary (44%) recipients. Comparison of molecular profiles of single hibernating LT-HSCs to freshly isolated counterparts showed a high degree of similarity, but also identified key factors dispensable for LT-HSC function in transplantation assays including members of the AP1 complex (Jun, Fos, and Ncor2), Sult1a1 and Cish.

2021-04-06 | GSE160131 | GEO

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

Project description:Small nucleolar RNA (snoRNA) are non-coding RNAs, which participate in the chemical modification of ribosomal RNAs (rRNAs) and small nuclear RNAs. However, the roles of snoRNA in homeostasis of hematopoietic stem cells(HSCs) have not been studied. We isolated four hematopoietic stem and progenitor cells (HSPCs) (LT-HSCs, IT-HSCs, ST-HSCs, and MPPs) from the bone marrow (BM) of C57BL/6 mice and performed small RNA-seq. We found SnoRNAs belonging to SNORD113-114 cluster were specifically enriched in LT-HSCs, and their expression decreased dramatically with HSC differentiation. To explore function of snoRNAs in SNORD113-114 cluster in HSCs, we established maternally KO mice by CRISPR-Cas9 technology. Here, we used a modified small RNA-seq method to examine snoRNA profile in KO mice.

2024-06-03 | GSE166517 | GEO

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