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Transcriptome of subsets of human haematopoietic stem cells from non-mobilised peripheral blood of healthy donors and CD71+ HSC/MPP

ABSTRACT: Transcriptome of subsets of human haematopoietic stem cells from non-mobilised peripheral blood of healthy donors and CD71+ HSC/MPP

PROVIDER: PRJNA789599 | ENA |

REPOSITORIES: ENA

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CD71+ HSC/MPP

Project description:CD71+ HSC/MPP

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CD71+ HSC/MPP

Project description:We describe the unique enrichment of erythroid-megakaryocyte primed CD71+ phenotypic HSC/MPPs in steady-state PB.

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Transcriptome of subsets of human haematopoietic stem cells from non-mobilised peripheral blood of healthy donors

Project description:Integration of index sorting and single cell functional assays identified two functionally distinct subsets of phenotypic haematopoietic stem cells and multipotent progenitors (HSC/MPPs) in the peripheral blood (PB) from healthy individuals. CD71- HSC/MPPs from PB are multipotent and can repopulate the NSG xenograft model. CD71+ HSC/MPPs are a subset of phenotypic HSC/MPPs that is uniquely restricted to give rise to erythroid and megakaryocytic lineages, and expands in conditions with chronic stimulation of platelet production (e.g. frequent platelet donation, idiopathic thrombocytopenic purpura, essential thrombocythaemia). Here, we report the bulk transcriptomes of pools of 20 cells from CD71- HSC/MPPs (CD19- CD38- CD45RA- CD34lo CD71-) and CD71+ HSC/MPPs (CD19- CD38- CD45RA- CD34lo CD71+). Altogether the data shows the transcriptional similarities and differences between both subsets. It shows, that the unique erythroid/megakaryocytic lineage-priming of CD71+ HSC/MPPs is already initiated at transcriptional level, and that CD71+ HSC/MPPs differ from CD71- HSC/MPPs with regards to their protein synthesis/metabolic pathways.

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Transcription profiling of Pairwise comparisons of purified mouse LT-HSC, ST-HSC and MPP

Project description:Pairwise comparisons of purified mouse LT-HSC, ST-HSC and MPP.

2005-09-09 | E-SMDB-3457 | biostudies-arrayexpress

Transcriptomic characterisation of phenotypic haematopoietic stem cells from human adult bone marrow, spleen and peripheral blood

Project description:Haematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), the precursors of all blood cells, reside predominantly in the bone marrow (BM). Recent evidence suggests that other anatomical sites may contribute significantly to blood production, but the cellular, molecular and functional composition of extramedullary HSC/MPP pools remains unexplored. Here, we have compared the transcriptomes of single cells sorted from the phenotypic HSC/MPP pool of adult bone marrows and spleens from the same donors.

2020-01-14 | GSE143567 | GEO

Transcriptome of subsets of human haematopoietic stem cells from non-mobilised peripheral blood of healthy donors and CD71+ HSC/MPP

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

2021-12-17 | GSE191085 | GEO

Transcriptome of cord blood derived subsets of human haematopoietic stem cells, LMPP and MLP myelo-lymphoid restricted progenitors [49f+ Subset2, Subset2, LMPPs, MLPs]

Project description:Integration of index sorting and single cell functional assays allowed identification of novel haematopoietic stem cell (HSC) and multiprogenitor subsets (MPP) that differ in their lineage differentiation potential in vitro and in vivo, cell cycle properties and long-term repopulation capacity in the NSG xenograft model. Here we report single cell transcriptomes of CD49f+ HSCs as well as those of CD49f+ Subset1 (CD19- CD38- CD45RA- CD90+ CD49f+ CD34lo CLEC9Ahi, Myelo-erythroid-skewed in vitro but Lymphoid-competent) and CD49f+ Subset2 cells (CD19- CD38- CD45RA- CD90+ CD49f+ CD34hi CLEC9Alo, Myelo-Lymphoid competent but Erythroid-deficient). We also report bulk transcriptomes of pools of 20 cells from HSC/MPP Subset1 (CD19- CD38- CD45RA- CD34lo CLEC9Ahi) and HSC/MPP Subset2 (CD19- CD38- CD45RA- CD34hi CLEC9Alo). Altogether these data show a diffuse transcriptional landscape of the CD49f+ HSC compartment, which is polarised along an axis that separates Myelo-Erythroid and Myelo-Lymphoid lineage-priming. Consistently with their differentiation capacity in vitro, CD49f+ Subset1 cells cluster at the Myelo-Erythroid end of the landscape, while CD49f+ Subset2 cells cluster at the Myelo-Lymphoid end. In addtion, these lineage-priming signatures were found to be more marked in HSC/MPP Subset1 and HSC/MPP Subset2, than in the equivalent CD49f+ subsets. In conclusion, 49f+ Subset1 and 49f+ Subset2 populations have activated distinct transcriptional lineage-priming programmes corresponding to the phenotypic lineage-skewing observed in vitro, that then become reinforced within the broader HSC/MPP pool. Altogether our data shows that lineage-priming and lineage-restriction programmes are initially established within the CD49f+ HSC subset in humans.

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DNA methylation in Vav-IDH1-KI mouse haematopoietic stem cells

Project description:Mutations in isocitrate dehydrogenase-1 (IDH1 R132) and -2 (IDH2 R140 and R172), which confer neomorphic enzymatic activity converting αKG (α-ketoglutarate) to D-2-hydroxyglutarate (D2HG), occur commonly in acute myeloid leukemia (AML). Mutant IDH1 alters epigenetics and increases haematopoietic progenitors in vivo, consistent with D2HG-mediated inhibition of TET2 5-methylcytosine hydroxylase. As TET2 mutations are mutually exclusive with IDH1/2 mutations and confer a similar phenotype, it has been widely believed that the oncogenicity of mutant IDH1/2 is due to TET2 inhibition. However, IDH1/2 mutations may have additional effects explaining the clinical features of MDS/MPN/AML. Here we show that mutant IDH1 downregulates ATM, thereby inhibiting DNA damage responses and increasing genomic instability. To investigate potential mechanisms of ATM downregulation, we examined ATM promoter DNA methylation in Vav-IDH1-KI long term haematopoietic stem cells (LT-HSC), short term haematopoietic stem cells (ST-HSC) and multipotent progenitors (MPP).

2017-08-23 | GSE66536 | GEO

Single cell transcriptomes of cord blood derived subsets of human haematopoietic stem cells, LMPP and MLP myelo-lymphoid restricted progenitors [49f+ HSCs, 49f+ Subset1, 49f+ Subset2, Subset1, Subset2]

2018-09-14 | GSE104995 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [10x]

Project description:Haematopoietic stem cells (HSC) and multipotent progenitor cells (MPP) generate all cells of the blood system, although cellular heterogeneity and bias in lineage potential have been observed. Here, we examined whether lineage-specific transcription factors, such as the B-lineage determinant EBF1, establish lineage bias in early progenitors. We detect low level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, and show that Ebf1-deficient animals display reduced HSC quiescence and repopulation capacity, enhanced myelopoiesis and enhanced myeloid differentiation potential of MPP3 and MPP4 cells. Bulk and single-cell RNA-seq analysis revealed a CEBPa-driven myeloid transcriptome in Ebf1-deficient progenitors, and we find that EBF1 binds and potentially antagonizes the haematopoietic Cebpa enhancer. In MPP3 cells, EBF1 additionally primes enhancers associated with B-lymphoid genes that gain expression in common lymphoid progenitors. Thus, our study identifies EBF1 as an important determinant in regulating the balance of myeloid versus lymphoid potential in the earliest hematopoietic progenitors.

2022-06-30 | GSE189051 | GEO

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