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Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics

ABSTRACT: Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics

PROVIDER: PRJNA1065394 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27562049.fastq.gz	Fastqsanger.gz
	SRR27562050.fastq.gz	Fastqsanger.gz
	SRR27562051.fastq.gz	Fastqsanger.gz
	SRR27562052.fastq.gz	Fastqsanger.gz
	SRR27562053.fastq.gz	Fastqsanger.gz

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Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics

Project description:Non-hematopoietic cells contribute essentially to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-Seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed Co-Detection by Indexing (CODEX) to spatially profile over one million single cells with a novel 53-antibody panel. We integrated scRNA-Seq and CODEX data to link cellular signaling and spatial proximity. Spatial analysis also revealed a hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, localization for early hematopoietic stem and progenitor cells. We used our CODEX atlas to automatically annotate cell types in new bone marrow images and uncovered MSC expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. This comprehensive, spatially-resolved multiomic atlas of human bone marrow serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

2024-04-24 | GSE253355 | GEO

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.

Project description:The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

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

Project description:We have previously shown that skull bone marrow derived myeloid cells are different from their blood derived counterparts. Whether or not cues from the CNS microenvironment differentially shape the skull bone marrow niche relative to peripheral bone marrow niches is unknown. To test this, we performed scRNAseq of skull and peripheral bone marrow niches.

2022-01-11 | GSE184766 | GEO

Characterization of Human Bone Marrow Niches with Metabolome and Transcriptome Profiling

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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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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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.

2023-06-30 | GSE228543 | GEO

Characterization of Human Bone Marrow Niches with Metabolome and Transcriptome Profiling

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

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Dissecting the cellular architecture of neuroblastoma bone marrow metastasis using single-cell transcriptomics and epigenomics

Project description:The bone marrow (BM) is the third most frequent site of metastasis for solid tumors, creating an unfavorable clinical outcome. It provides a unique microenvironment that promotes growth of tumors, however, the role of different BM cells, their molecular features, and their interactions with tumor cells, are poorly defined. Here, we investigate the BM niche in neuroblastoma (NB), a pediatric cancer of the sympathetic nervous system. NB has been molecularly defined at the primary cancer site, yet, the metastatic site is poorly characterized. We performed single-cell transcriptomics (scRNA-seq) and epigenomic profiling (scATAC-seq) of BM aspirates from 11 subjects spanning three major NB subtypes: patients with MYCN amplification (MNA), ATRX mutations (ATRXmut), and cases that lack these alterations (sporadic): NB cases were then compared to five age-matched and metastasis-free BM (controls), followed by in-depth single cell analyses of tissue diversity and cell-cell interactions. We present the first map of the epigenetic and transcriptomic effects of bone marrow metastases. Our analyses demonstrate that tumor cells in the metastatic niche display plasticity that differs among NB subtypes. NB cells via cell-cell interaction signal to the bone marrow microenvironment, rewiring specifically monocytes, which exhibit M1 and M2 features, marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. Our study may provide the basis for a therapeutic approach, targeting tumor-to-microenvironment interactions.

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