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Mus musculus

ABSTRACT: Lympho-myeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells

PROVIDER: PRJNA219339 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1781890.fastq.gz	Fastqsanger.gz
	SRR1781900.fastq.gz	Fastqsanger.gz
	SRR1781891.fastq.gz	Fastqsanger.gz
	SRR1781901.fastq.gz	Fastqsanger.gz
	SRR1781892.fastq.gz	Fastqsanger.gz

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Lympho-myeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells

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Lympho-myeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells

Project description:An immune-restricted lymphomyeloid-primed progenitor with the capacity to contribute to both myeloid and lymphoid lineages in the developing embryo emerges prior to definitive HSCs. Examination of fetal sorted lymphoid primed progentors and adult progenitors The fastq files are not provided at this time due to further analyses.

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Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy [CITE-seq]

Project description:The advent of single cell (Sc) genomics has challenged the dogma of haematopoiesis as a tree-like structure of stepwise lineage commitment through distinct and increasingly restricted progenitor populations. Instead, analysis of ScRNA-seq has proposed that the earliest events in human hematopoietic stem cell (HSC) differentiation are characterized by only subtle molecular changes, with hematopoietic stem and progenitor cells (HSPCs) existing as a continuum of low-primed cell-states that gradually transition into a specific lineage (CLOUD-HSPCs). Here, we combine ScRNA-seq, ScATAC-seq and cell surface proteomics to dissect the heterogeneity of CLOUD-HSPCs at different stages of human life. Within CLOUD-HSPCs, pseudotime ordering of both mRNA and chromatin data revealed a bifurcation of megakaryocyte/erythroid and lympho/myeloid trajectories immediately downstream a subpopulation with an HSC-specific enhancer signature. Importantly, both HSCs and lineage-restricted progenitor populations could be prospectively isolated based on correlation of their molecular signatures with CD35 and CD11A expression, respectively. Moreover, we describe the changes that occur in this heterogeneity as hematopoiesis develops from neonatal to aged bone marrow, including an increase of HSCs and depletion of lympho-myeloid biased MPPs. Thus, this study dissects the heterogeneity of human CLOUD-HSPCs revealing distinct HSPC-states of relevance in homeostatic settings such as ageing.

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Project description:Initial seeding of the embryonic thymus by an immune-restricted lympho-myeloid progenitor independently of Notch signaling

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Single-cell RNA sequencing of EPLM subpopulations (152 Ly6D+ and 213 TN)

Project description:Single-cell RNA-sequencing has emerged as a powerful technology to assess heterogeneity within defined cell populations. Here, we comprehensively study the heterogeneity of a previously described B220+CD117intCD19-NK1.1- uncommitted hematopoietic progenitor with combined lymphoid and myeloid potential (EPLM). Using staining for surface markers together with functional assays, we describe four subpopulations of this progenitor with distinct lineage developmental potentials. Amongst them, the Ly6D+SiglecH-CD11c- fraction was lymphoid restricted exhibiting strong B-cell potential, whereas the Ly6D-SiglecH-CD11c- fraction showed mixed lympho-myeloid potential. Single-cell RNA-sequencing of these subsets revealed that the latter population is composed of a mixture of cells with distinct lymphoid and myeloid genetic signatures and identified a subgroup as the potential precursor of Ly6D+SiglecH-CD11c-. We observed a B-cell priming gradient within the Ly6D+SiglecH-CD11c- subset and propose a herein newly identified subgroup as the direct precursor of the first B-cell committed stage. Our study demonstrates that the multipotency of B220+CD117intCD19-NK1.1- progenitors is a result of underlying heterogeneity at the single-cell level. Moreover, it highlights the validity of single-cell transcriptomics to resolve cellular heterogeneity and identify developmental relationships in hematopoietic progenitors.

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Mitochondrial activity dictates definitive hematopoietic stem cell production and lympho-myeloid lineage segregation during mouse embryogenesis [scRNAseq]

Project description:Mitochondrial activity dictates definitive hematopoietic stem cell production and lympho-myeloid lineage segregation during mouse embryogenesis [scRNAseq]

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Expression data from control and Pbx1-null CMPs and GMPs

Project description:The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs). Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, we demonstrate that in the absence of Pbx1 the CMP pool is reduced due to aberrantly rapid myeloid maturation, associated with decreased expression of Meis1 and its targets including Flt3. BM cells were obtained from multiple bones of individual three to five week old Tie2Cre+.Pbx1-/f or Tie2Cre+.Pbx1+/f control mice (4-5 biological replicates/group). CMPs and GMPs were sorted by flow cytometry according to the following markers: Lin-/c-Kit+/Sca-/CD34+/CD16/32int, and Lin-/c-Kit+/Sca-/CD34+/CD16/32high, respectively, prior to RNA extraction.

2013-03-31 | E-GEOD-30028 | biostudies-arrayexpress

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