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High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-PBMC-invivo-scATAC]

ABSTRACT: High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-PBMC-invivo-scATAC]

PROVIDER: PRJNA624787 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11539031_1.fastq.gz	Fastqsanger.gz
	SRR11539031_2.fastq.gz	Fastqsanger.gz
	SRR11539032_1.fastq.gz	Fastqsanger.gz
	SRR11539032_2.fastq.gz	Fastqsanger.gz
	SRR11539033_1.fastq.gz	Fastqsanger.gz

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High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-PBMC-invivo-scATAC]

Project description:Natural mitochondrial DNA (mtDNA) sequence variation plays a fundamental role in human disease and enables the clonal tracing of native human cells. While various genotyping approaches revealed mutational heterogeneity in human tissues and single cells, current methodologies are limited by scale. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell Assay for Transposase Accessible Chromatin with sequencing (mtscATAC-seq) protocol and computational framework that facilitate high-confidence mtDNA mutation calling in thousands of single cells. Further, the concomitant high-quality accessible chromatin readout enables the paired inference of individual cell mtDNA heteroplasmy, clonal lineage, cell state, and accessible chromatin regulatory features. Our multi-omic analyses reveals single-cell variation in heteroplasmy of a pathologic mtDNA variant (m.8344A>G), which we tie to intra-individual chromatin variability and clonal evolution. Further, using somatic mtDNA mutations, we clonally trace thousands of hematopoietic cells in vitro and in patients with chronic lymphocytic leukemia, linking epigenomic variability to subclonal evolution in vivo.

2020-07-13 | GSE148508 | GEO

High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CLL-scATAC]

Project description:High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CLL-scATAC]

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High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-invitro]

Project description:High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-invitro]

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scATAC-seq of mouse Plasmodium-specific CD4+ T cells

Project description:Plasmodium-specific CD4+ T cells from mice infected with Plasmodium chabaudi chabaudi AS parasites were recovered at Days 0, 4, 7, and 32 to undergo processing and to generate scATAC-seq dataset. At Day 7, CXCR5+ and CXCR6+ cells were recovered separately. At Day 32, mice were administered with either saline or artesunate (intermittent artesunate therapy - IAT). scATAC-seq dataset was analysed to investigate epigenomic landscapes of CD4+ T cells from effector to memory states.

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Project description:During the course of many chronic inflammatory disorders, a persistent Natural Killer (NK) cell derangement and activation is observed. While increased cell turnover is expected in these cases, little is known about whether and how NK cell homeostatic balance and numbers are maintained by CD34+ progenitor cells. Accordingly, we studied peripheral blood progenitor cells in patients with chronic inflammatory disorders including HIV-1, HCV, TB, COPD and PAPA. Cytometric analysis revealed the presence of a so far unidentified CD34+CD226(DNAM-1)brightCXCR4+ cell population in all these conditions. Further, microarray and PCR analysis showed transcriptional signatures typical of common lymphocyte precursors. Culture of CD34+CD226brightCXCR4+ cells gave rise to NK cell progenies characterized by high expression of activating receptors and mature function. Importantly, in healthy donors CD34+CD226brightCXCR4+ cells reside in bone marrow but do not circulate in peripheral blood and are absent in umbilical cord blood. The proportion of CD34+CD226brightCXCR4+ PBMC were found to correlate with the degree of inflammation, and represent an indicator of lymphoid cell turnover/reconstitution during chronic inflammation. Identification of CD34+CD226brightCXCR4+ circulation offers a novel view of emergency recruitment of cell-precursors upgrade our understanding and monitoring of chronic inflammatory conditions, and provide new insight of intermediate stages of NK cell development.

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