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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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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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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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A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

Project description:Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We show that within the canonical Lin-CD34+CD38dim/loCD90-CD45RA- MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69- erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2- LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe limited cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing new adult MPP sub-populations, we provide an updated reference and framework for future studies in human hematopoiesis.

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Common lymphoid progenitor-independent pathways of innate and T lymphocyte development

Project description:All lymphocytes are thought to develop from common lymphoid progenitors (CLPs). However, lymphoid-primed multi-potent progenitors (LMPPs) are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s). Here, we have divided LMPPs into CD127− (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with Ly6D− and Ly6D+ CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long-lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways.

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