Header

UZH-Logo

Maintenance Infos

Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization


Baccin, Chiara; Al-Sabah, Jude; Velten, Lars; Helbling, Patrick M; Grünschläger, Florian; Hernández-Malmierca, Pablo; Nombela-Arrieta, César; Steinmetz, Lars M; Trumpp, Andreas; Haas, Simon (2020). Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nature Cell Biology, 22(1):38-48.

Abstract

The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This allowed us to transcriptionally profile all major bone-marrow-resident cell types, determine their localization and clarify sources of pro-haematopoietic factors. Our data demonstrate that Cxcl12-abundant-reticular (CAR) cell subsets (Adipo-CAR and Osteo-CAR) differentially localize to sinusoidal and arteriolar surfaces, act locally as 'professional cytokine-secreting cells' and thereby establish peri-vascular micro-niches. Importantly, the three-dimensional bone-marrow organization can be accurately inferred from single-cell transcriptome data using the RNA-Magnet algorithm described here. Together, our study reveals the cellular and spatial organization of bone marrow niches and offers a systematic approach to dissect the complex organization of whole organs.

Abstract

The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This allowed us to transcriptionally profile all major bone-marrow-resident cell types, determine their localization and clarify sources of pro-haematopoietic factors. Our data demonstrate that Cxcl12-abundant-reticular (CAR) cell subsets (Adipo-CAR and Osteo-CAR) differentially localize to sinusoidal and arteriolar surfaces, act locally as 'professional cytokine-secreting cells' and thereby establish peri-vascular micro-niches. Importantly, the three-dimensional bone-marrow organization can be accurately inferred from single-cell transcriptome data using the RNA-Magnet algorithm described here. Together, our study reveals the cellular and spatial organization of bone marrow niches and offers a systematic approach to dissect the complex organization of whole organs.

Statistics

Citations

Dimensions.ai Metrics
40 citations in Web of Science®
39 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Cell Biology
Language:English
Date:January 2020
Deposited On:20 Oct 2020 09:49
Last Modified:21 Oct 2020 20:00
Publisher:Nature Publishing Group
ISSN:1465-7392
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41556-019-0439-6
PubMed ID:31871321

Download

Full text not available from this repository.
View at publisher

Get full-text in a library