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

被引：581

作者：

Baccin, Chiara ^{[1
,2
,3
]}

Al-Sabah, Jude ^{[4
,5
,6
]}

Velten, Lars ^{[1
,12
]}

Helbling, Patrick M. ^{[7
,8
]}

Gruenschlaeger, Florian ^{[4
,5
,6
]}

Hernandez-Malmierca, Pablo ^{[4
,5
,6
]}

Nombela-Arrieta, Cesar ^{[7
,8
]}

Steinmetz, Lars M. ^{[1
,9
,10
]}

Trumpp, Andreas ^{[4
,5
,6
,11
]}

Haas, Simon ^{[4
,5
,6
]}

机构：

[1] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany

[2] EMBL, Fac Biosci, Heidelberg, Germany

[3] Heidelberg Univ, Heidelberg, Germany

[4] Heidelberg Inst Stem Cell Technol & Expt Med HIST, Heidelberg, Germany

[5] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, Heidelberg, Germany

[6] DKFZ ZMBH Alliance, Heidelberg, Germany

[7] Univ Hosp, Dept Med Oncol & Hematol, Zurich, Switzerland

[8] Univ Zurich, Zurich, Switzerland

[9] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[10] Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

[11] German Canc Consortium DKTK, Heidelberg, Germany

[12] Barcelona Inst Sci & Technol, Ctr Genom Regulat, Barcelona, Spain

来源：

NATURE CELL BIOLOGY | 2020年 / 22卷 / 01期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

HEMATOPOIETIC STEM-CELLS; MAP; RECONSTRUCTION; EXPRESSION; PROMOTE; GROWTH;

D O I：

10.1038/s41556-019-0439-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：38 / +

页数：26

共 59 条

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