Microbiota-derived lactate promotes hematopoiesis and erythropoiesis by inducing stem cell factor production from leptin receptor plus niche cells
- Abstract
- 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.
Blood cell formation: Support from gut bacteria Lactic acid produced by microbes in the gut has been implicated in supporting the production of blood cells, suggesting oral administration of lactic acid-producing bacteria might be useful for treating blood disorders, including anemia. Researchers in South Korea and China, led by Mi-Na Kweon at the University of Ulsan in Seoul, explored the significance of lactic acid using mice deficient in the gene for a protein receptor that allows lactic acid to influence various cellular processes. Without the benefit of this receptor the levels of blood cell-forming stem cells in bone marrow were reduced. The normal effect of lactic acid was linked to production of a protein called stem cell factor in specific cells. Oral administration of lactic acid-producing bacteria restored blood cell formation, indicating its therapeutic potential.
- Author(s)
- 이용수; 김태영; 김예지; 김승일; 이수현; 서상욱; Bo O. Zhou; 오은주; 김광순; 권미나
- Issued Date
- 2021
- Type
- Article
- Keyword
- Microbiota; Lactate; Stem cell Factor; LepR; GPR81
- DOI
- 10.1038/s12276-021-00667-y
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/7318
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_9859969&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Microbiota-derived%20lactate%20promotes%20hematopoiesis%20and%20erythropoiesis%20by%20inducing%20stem%20cell%20factor%20production%20from%20leptin%20receptor%20plus%20niche%20cells&offset=0&pcAvailability=true
- Publisher
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Location
- 영국
- Language
- 한국어
- ISSN
- 1226-3613
- Citation Volume
- 53
- Citation Number
- 9
- Citation Start Page
- 1319
- Citation End Page
- 1331
-
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