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Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion [Long-term hematopoietic stem cells, LT-HSCs]

ABSTRACT: Latexin is a hematopoietic stem cell (HSC) regulatory gene. Its deletion leads to the expansion of HSC population. The underlying mechanims are largely unknown. We therefore perfored microarrary analysis in HSCs with (Lxn-/-) and without (wild-type, WT) latexin deletion, and determined genes that were altered by latexin deletion. This led us to identify the molecular mechanims by which latexin regulates HSC function.

ORGANISM(S): Mus musculus

PROVIDER: GSE94663 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA371781

REPOSITORIES: GEO

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Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion [multipotent progenitor cells, MPPs]

Project description:Latexin is a hematopoietic stem cells (HSCs) and progenitor cells (HPCs) regulatory gene. Its deletion leads to the expansion of HSC and HPC population. The underlying mechanims are largely unknown. We therefore perfored microarrary analysis in HPCs with (Lxn-/-) and without (wild-type, WT) latexin deletion, and determined genes that were altered by latexin deletion. This led us to identify the molecular mechanims by which latexin regulates HSC function.

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Time-course analysis of transcriptomes of human long-term (LT) and short-term (ST) hematopoietic stem cells (HSC) after xenotransplantation

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

Time-course analysis of transcriptomes of human long-term (LT) and short-term (ST) hematopoietic stem cells (HSC) after xenotransplantation

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RNA-seq of uncultured CD112high and CD112low and cultured long-term (LT) and short-term (ST) human hematopoietic stem cells (HSC) overexpressing INKA-1

Project description:RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

2021-03-25 | GSE148883 | GEO

Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice.

Project description:Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1) was a potential downstream target with a dramatic downregulation in Lxn-null HSCs. Enforced expression of Thbs1 restored the Lxn inactivation-mediated HSC phenotypes. This study reveals that Lxn plays an important role in the maintenance of homeostatic hematopoiesis, and it may lead to development of safe and effective approaches to manipulate HSCs for clinical benefit.

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ATAC-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) from umbilical cord blood

Project description:We performed ATAC-sequencing to elucidate the chromatin accessibility that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated these subpopulations from 3 independent human umbilical cord blood pools and subjected to ATAC-sequencing directly. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 and low H4K16ac preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

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Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion

Project description:Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion

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Project description:We aimed to reseach the differences between IL4Rα high and low expression LT-HSC/CMP,our data revealed distinct sensitivities of HSCs and common myeloid progenitors (CMPs) to IL4-induced apoptosis, and IL4Rahigh HSCs were more susceptible to unfolded protein response (UPR) and irradiation-induced apoptosis.

2020-06-25 | GSE109324 | GEO

Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-09 | GSE94665 | GEO

Next Generation Sequencing of long-term hematopoietic cells (LT-HSCs) with or without mutations in JAK2 and Ezh2

Project description:Comparison of mRNA expression profiles of LT-HSCs with or without mutations in JAK2 and Ezh2 by RNA sequencing. LT-HSC mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of LT-HSC with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. Our results revealed that mRNA expression profile of LT-HSC with different genotype showed specific gene expression patterns, which allows to do biological comprehensive and quantitative analysis for hematopoiesis. LT-HSCs mRNA profiles six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) were generated by deep sequencing.

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