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Mus musculus

ABSTRACT: Single Novel single cell assay reveals progressive lymphoid defect in aging multipotent hematopoietic progenitors cell RNA-seq reveals LMPP clonal dynamics in aging.

PROVIDER: PRJNA311330 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3157490_1.fastq.gz	Fastqsanger.gz
	SRR3157490_2.fastq.gz	Fastqsanger.gz
	SRR3157500_1.fastq.gz	Fastqsanger.gz
	SRR3157500_2.fastq.gz	Fastqsanger.gz
	SRR3157510_1.fastq.gz	Fastqsanger.gz

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Mus musculus

Project description:Single Novel single cell assay reveals progressive lymphoid defect in aging multipotent hematopoietic progenitors cell RNA-seq reveals LMPP clonal dynamics in aging.

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Project description:Single Novel single cell assay reveals progressive lymphoid defect in aging multipotent hematopoietic progenitors Cell RNA-seq reveals LMPP clonal dynamics in aging.

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Single Novel single cell assay reveals progressive lymphoid defect in aging multipotent hematopoietic progenitors Cell RNA-seq reveals LMPP clonal dynamics in aging.

Project description:Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of the dynamic changes with age in the heterogeneous multipotent hematopoietic progenitor cell compartment, which regulates output of differentiated lymphoid cells. In this study, we observed progressive and specific loss of lymphoid-primed multipotent progenitor cells (LMPP/MPP4) as young animals began to age. Single cell RNA-seq revealed a concomitant increase in cycling of these progenitors with loss of a lymphoid priming signature. To interrogate functional multipotency of single cells, we developed a novel, feeder-free in vitro assay to concurrently assess lymphoid and myeloid potential. This assay revealed altered clonal composition of the LMPP/MPP4 compartment with aging, where progenitors with B cell and macrophage-restricted potential are lost while functionally multipotent progenitors are preserved. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging.

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Project description:Regulation of lineage potential and transcriptional priming by Ikaros. New insight is provided into a bivalent regulation of lineage priming in the HSC and its lympho-myeloid restricted progeny the LMPP by the lymphoid lineage-determining factor Ikaros; Whereas Ikaros is responsible for the activation of a cascade of lymphoid expression programs and for the establishment of lymphoid potential from the HSC to the LMPP it is also responsible for the repression of stem cell and erythroid genetic programs that are incompatible with further lineage restrictions emanating from the LMPP Experiment Overall Design: Ikaros null versus wt

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