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Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE174040 | GEO | 2022/05/20

REPOSITORIES: GEO

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Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [WES]

Project description:We transplanted a single HSC into irradiated mice, creating a clonal hematopoietic system. This allowed us to study mitotically stable allelic imbalances at peripheral compartments (T cells, B cells).

2022-05-20 | GSE174039 | GEO

Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [RNA-seq]

Project description:We transplanted a single HSC into irradiated mice, creating a clonal hematopoietic system. Using RNA-Seq on the cDNA of the peripheral compartments (T cells, B cells), we studied mitotically stable transcriptional states of the alleles of the entire transcriptome on the differentiating HSC.

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Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system

Project description:Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system

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Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [WES]

Project description:Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [WES]

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Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [RNA-seq]

Project description:Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system [RNA-seq]

| PRJNA728046 | ENA

Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence.

Project description: Not available

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Single-cell transcriptomics of murine mural cells reveals cellular heterogeneity.

Project description:Mural cells (MCs) wrap around the endothelium, and participate in the development and homeostasis of vasculature. MCs have been reported as heterogeneous population morphologically and functionally. However, the transcriptional heterogeneity of MCs was rarely studied. In this study, we illustrated the transcriptional heterogeneity of MCs with different perspectives by using publicly available single-cell dataset GSE109774. Specifically, MCs are transcriptionally different from other cell types, and ligand-receptor interactions of different cells with MCs vary. Re-clustering of MCs identified five distinct subclusters. The heterogeneity of MCs in tissues was reflected by MC coverage, various distribution of MC subclusters, and ligand-receptor interactions of MCs and parenchymal cells. The transcriptomic diversity of MCs revealed in this article will help facilitate further research into MCs.

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Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies.

Project description:BackgroundChromosome instability leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes, and is found in two out of three cancers. In a chromosomal instable p53 deficient mouse model with accelerated lymphomagenesis, we previously observed whole chromosome copy number changes affecting all lymphoma cells. This suggests that chromosome instability is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes out-competes the CIN-imposed mis-segregation.ResultsTo distinguish between these explanations and to examine karyotype dynamics in chromosome instable lymphoma, we use a newly developed single-cell whole genome sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. To analyse these scWGS data, we develop AneuFinder, which allows annotation of copy number changes in a fully automated fashion and quantification of CNV heterogeneity between cells. Single-cell sequencing and AneuFinder analysis reveals high levels of copy number heterogeneity in chromosome instability-driven murine T-cell lymphoma samples, indicating ongoing chromosome instability. Application of this technology to human B cell leukaemias reveals different levels of karyotype heterogeneity in these cancers.ConclusionOur data show that even though aneuploid tumours select for particular and recurring chromosome combinations, single-cell analysis using AneuFinder reveals copy number heterogeneity. This suggests ongoing chromosome instability that other platforms fail to detect. As chromosome instability might drive tumour evolution, karyotype analysis using single-cell sequencing technology could become an essential tool for cancer treatment stratification.

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TRACE-Seq Reveals Clonal Reconstitution Dynamics of Gene Targeted Human Hematopoietic Stem Cells

Project description:We present Tracking Recombination Alleles in Clonal Engraftment using sequencing (TRACE-Seq), a novel methodology that utilizes barcoded rAAV6 donor template libraries, carrying either in-frame silent mutations or semi-randomized nucleotide sequences outside the coding region, to track the in vivo lineage contribution of gene targeted HSPC clones. By targeting the HBB gene with a rAAV6 donor template library consisting of ~20,000 possible unique exon 1 in-frame silent mutations, we track the hematopoietic reconstitution of HBB targeted myeloid-only, lymphoid-only, and multi-lineage repopulating human HSPC clones in immunodeficient mice.

2020-08-09 | GSE155910 | GEO

Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging.

Project description:In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow and are in part regulated by the bone marrow microenvironment, called the stem cell niche. We have previously identified the bone marrow morphogen osteopontin (OPN), which is abundantly present in the bone marrow extracellular matrix, as a negative regulator of the size of the HSC pool under physiological conditions. Here, we study the impact of OPN on HSC function during aging using an OPN-knockout mouse model. We show that during aging OPN deficiency is associated with an increase in lymphocytes and a decline in erythrocytes in peripheral blood. In a bone marrow transplantation setting, aged OPN-deficient stem cells show reduced reconstitution ability likely due to insufficient differentiation of HSCs into more mature cells. In serial bone marrow transplantation, aged OPN-/- bone marrow cells fail to adequately reconstitute red blood cells and platelets, resulting in severe anemia and thrombocytopenia as well as premature deaths of recipient mice. Thus, OPN has different effects on HSCs in aged and young animals and is particularly important to maintain stem cell function in aging mice.

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