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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses

ABSTRACT: Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses

PROVIDER: PRJNA962176 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24318900.fastq.gz	Fastqsanger.gz
	SRR24319000.fastq.gz	Fastqsanger.gz
	SRR24319100.fastq.gz	Fastqsanger.gz
	SRR24318901.fastq.gz	Fastqsanger.gz
	SRR24319001.fastq.gz	Fastqsanger.gz

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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses [scVDJ-seq]

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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses [scRNA-Seq]

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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses [scVDJ-seq]

Project description:Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4. Additional clusters included IgM-predominant ASC of likely extra-follicular origin; IFN-responsive; and high mitochondrial activity ASC. Late ASCs were distinguished by differences in G2M checkpoints, MTOR signaling, distinct metabolic pathways, CD38 expression, and utilization of TNF-receptor superfamily members. They mature through two distinct paths differentiated by the degree of TNF signaling through NFKB. This study provides the first single cell resolution atlas and molecular roadmap of LLPC maturation, thereby providing insight into differentiation trajectories and molecular regulation of these essential processes in the human BM microniche. This information enables investigation of the origin of protective and pathogenic antibodies in multiple diseases and development of new strategies targeted to the enhancement or depletion of the corresponding ASC.

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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses [scRNA-Seq]

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Project description:Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASCs) to long-lived plasma cells (LLPCs). We provide single-cell transcriptional resolution of 17,347 BM ASCs from five healthy adults. Fifteen clusters are identified ranging from newly minted ASCs (cluster 1) expressing MKI67 and high major histocompatibility complex (MHC) class II that progress to late clusters 5-8 through intermediate clusters 2-4. Additional ASC clusters include the following: immunoglobulin (Ig) M predominant (likely of extra-follicular origin), interferon responsive, and high mitochondrial activity. Late ASCs are distinguished by G2M checkpoints, mammalian target of rapamycin (mTOR) signaling, distinct metabolic pathways, CD38 expression, utilization of tumor necrosis factor (TNF)-receptor superfamily members, and two distinct maturation pathways involving TNF signaling through nuclear factor κB (NF-κB). This study provides a single-cell atlas and molecular roadmap of LLPC maturation trajectories essential in the BM microniche. Altogether, understanding BM ASC heterogeneity in health and disease enables development of new strategies to enhance protective ASCs and to deplete pathogenic ones.

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Maturation of Long Lived Plasma cells

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Understanding Heterogeneity of Human Bone Marrow Plasma Cell Maturation and Survival Pathways by Single Cell Analyses

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Affinity maturation of antibody responses is mediated by differential plasma cell proliferation

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