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KMID : 0620920210530091319
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Experimental & Molecular Medicine
2021 Volume.53 No. 9 p.1319 ~ p.1331
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Microbiota-derived lactate promotes hematopoiesis and erythropoiesis by inducing stem cell factor production from leptin receptor+ niche cells
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Lee Yong-Soo
Kim Tae-Young
Kim Ye-Ji
Kim Seung-Il
Lee Su-Hyun
Seo Sang-Uk
Zhou Bo O.
O. Eunju
Kim Kwang-Soon
Kweon Mi-Na
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Abstract
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Although functional interplay between intestinal microbiota and distant sites beyond the gut has been identified, the influence of microbiota-derived metabolites on hematopoietic stem cells (HSCs) remains unclear. This study investigated the role of microbiota-derived lactate in hematopoiesis using mice deficient in G-protein-coupled receptor (Gpr) 81 (Gpr81?/?), an established lactate receptor. We detected significant depletion of total HSCs in the bone marrow (BM) of Gpr81?/? mice compared with heterogenic (Gpr81+/?) mice in a steady state. Notably, the expression levels of stem cell factor (SCF), which is required for the proliferation of HSCs, decreased significantly in leptin receptor-expressing (LepR+) mesenchymal stromal cells (MSCs) around the sinusoidal vessels of the BM from Gpr81?/? mice compared with Gpr81+/? mice. Hematopoietic recovery and activation of BM niche cells after irradiation or busulfan treatment also required Gpr81 signals. Oral administration of lactic acid-producing bacteria (LAB) activated SCF secretion from LepR+ BM MSCs and subsequently accelerated hematopoiesis and erythropoiesis. Most importantly, LAB feeding accelerated the self-renewal of HSCs in germ-free mice. These results suggest that microbiota-derived lactate stimulates SCF secretion by LepR+ BM MSCs and subsequently activates hematopoiesis and erythropoiesis in a Gpr81-dependent manner.
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KEYWORD
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Immunology, Stem-cell research
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