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Microbiota-derived lactate promotes hematopoiesis and erythropoiesis by inducing stem cell factor production from leptin receptor plus niche cells

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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)
이용수김태영김예지김승일이수현서상욱Bo O. Zhou오은주김광순권미나
Issued Date
2021
Type
Article
Keyword
MicrobiotaLactateStem cell FactorLepRGPR81
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
Appears in Collections:
Medicine > Medicine
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