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Bone marrow niches orchestrate stem cell hierarchy and immune tolerance

ABSTRACT: Bone marrow niches orchestrate stem cell hierarchy and immune tolerance

PROVIDER: PRJNA1163324 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30735439_1.fastq.gz	Fastqsanger.gz
	SRR30735439_2.fastq.gz	Fastqsanger.gz
	SRR30735440_1.fastq.gz	Fastqsanger.gz
	SRR30735440_2.fastq.gz	Fastqsanger.gz
	SRR30735441_1.fastq.gz	Fastqsanger.gz

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Bone marrow niches orchestrate stem cell hierarchy and immune tolerance

Project description:Stem cells reside in specialized microenvironments, termed niches, at several different locations within tissues1-3. The differential functions of heterogeneous stem cells and niches are important given increasing clinical applications of stem cell transplantation and immunotherapy. It remains unknown whether hierarchical structures amongst stem cells at distinct niches exist, and further control aspects of immune tolerance. Here, we propose novel hierarchical arrangements within hematopoietic stem cells (HSCs) and bone marrow (BM) niches, that dictate both regenerative potential and immune privilege. High level nitric oxide-generating (NOHi) HSCs are refractory to immune attack and exhibit "delayed" albeit robust long-term reconstitution. Such highly immune privileged, primitive NOHi HSCs colocalize with distinctive capillaries, characterized by primary ciliated endothelium and high levels of the immune checkpoint molecule CD200. These capillaries regulate the regenerative functions of NOHi HSCs through ciliary protein IFT20/CD200/eNOS/autophagy signals, further mediating immune protection. Notably, previously described niche constituents, sinusoidal cells and Type H vessels2-10, co-localize with less immune privileged and less potent NOLow HSCs. Therefore, we have identified highly immune privileged, "late-rising" primitive HSCs and characterized their immunoprotective niches constituted of specialized vascular domains. Our studies suggest the niche may orchestrate hierarchy in stem cells and immune tolerance, delineating future immunotherapeutic targets.

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Distinct prefrontal projections oppositely orchestrate social competition and hierarchy

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Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels

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Project description:The hematopoietic niches in bone marrow (BM) are specialized compartments working in harmony to regulate all the steps of the hematopoiesis cascade. Little is known about how BM niches in healthy humans. Therefore, we investigated the presence of different niches in healthy human BM using comparative omic technologies (Metabolomic and transcriptomic). We sequenced and comparative analyzed mRNA samples of human bone marrow mesenchymal stem cells (MSCs) to generate the gene expression profiles of these cells which obtained from two anatomically different BM regions (R1 and R2).

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Isotype-based plasma cell subsets display differential niches requirements in the bone marrow

Project description:Bone marrow long-lived plasma cells are essential for long-term protection against infection and their persistence within this organ relies on interactions with Cxcl12-expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses we identified LepR+ mesenchymal cells as the stromal cell subset most likely to interact with plasma cells within the bone marrow. Moreover, we demonstrated that depending on the isotype they express, plasma cells may use different set of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of plasma cell subset stromal niches and open new avenues for the specific targeting of bone marrow plasma cells based on their isotype.

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Project description:Characterization of Human Bone Marrow Niches with Metabolome and Transcriptome Profiling

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Project description:The bone tissue undergoes constant turnover, which relies on skeletal stem cells (SSCs) and/or mesenchymal stem cells (MSCs) and their niches. SSCs/MSCs and their perivascular niche within the bone marrow are well characterized in long bones. As for cranial bones, besides bone marrow, the suture mesenchyme has been identified as a unique niche for SSCs/MSCs of craniofacial bones. However, a comprehensive study of the two different cranial stem cell niches at single-cell resolution is still lacking. In addition, during the progression of aging, age-associated changes in cranial stem cell niches and resident cells remain uncovered. In this study, we investigated age-related changes in cranial stem cell niches via single-cell RNA sequencing (scRNA-seq).

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