Dataset Information


RNA-seq analysis of bone marrow peri-vascular stromal cells

ABSTRACT: Fate decisions of haematopoietic stem cells (HSCs) to self-renew or differentiate in response to various demands are finely tuned by specialized microenvironments called “niches” in the bone marrow. Recent studies suggest that arterioles and sinusoids accompanied with distinct stromal cells marked by nerve/glial antigen 2 (NG2) and leptin receptor (LepR), compose distinct niches regulating quiescence and proliferation of HSCs, respectively. However, it remains unknown how the distinct niche cells differentially regulate the HSC functions. Here we show that effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (CXCL12) in NG2-cre targeted cells, which exclusively overlap with Nestin-GFP (Nes-GFP)+ stromal cells associated with arterioles and sinusoids, resulted in a robust reductions of HSCs in the bone marrow and massive mobilization. Deletion of CXCL12 from arteriolar NG2+ vascular smooth muscle cells caused a significant decrease of HSCs and altered HSC location in the marrow, while CXCL12 depletion from sinusoidal LepR+ cells did not reduce HSC numbers in the bone marrow. By contrast, deletion of stem cell factor (SCF) in LepR+ cells led to significant reductions in HSC numbers whereas SCF deletion in arteriolar NG2+ cells showed no effect on HSC numbers in the marrow. These results uncover the distinct contributions of cytokines derived from perivascular cells in separate vascular niches for HSC maintenance and mobilization. We sought to obtain comprehensive understanding of differences between peri-arteriolar and peri-sinusoidal niche cells by the present RNA-seq analysis. Overall design: mRNA profiles of sorted LepR-cre/Tomato+, NG2-cre/Tomato+, Myh11-creER/Tomato+, and CD31+ bone marrow stromal cells were generated by illumina HiSeq2500.

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Paul S Frenette 

PROVIDER: GSE89811 | GEO | 2017-02-19



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Differential cytokine contributions of perivascular haematopoietic stem cell niches.

Asada Noboru N   Kunisaki Yuya Y   Pierce Halley H   Wang Zichen Z   Fernandez Nicolas F NF   Birbrair Alexander A   Ma'ayan Avi A   Frenette Paul S PS  

Nature cell biology 20170220 3

Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand  ...[more]

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