title: Microbiota from Obese Mice Regulate Hematopoietic Stem Cell Differentiation by Altering the Bone Niche.
abstract: The effect of metabolic stress on the bone marrow microenvironment is poorly defined. We show that high-fat diet (HFD) decreased long-term Lin(-)Sca-1(+)c-Kit(+) (LSK) stem cells and shifted lymphoid to myeloid cell differentiation. Bone marrow niche function was impaired after HFD as shown by poor reconstitution of hematopoietic stem cells. HFD led to robust activation of PPARγ2, which impaired osteoblastogenesis while enhancing bone marrow adipogenesis. At the same time, expression of genes such as Jag-1, SDF-1, and IL-7 forming the bone marrow niche was highly suppressed after HFD. Moreover, structural changes of microbiota were associated to HFD-induced bone marrow changes. Antibiotic treatment partially rescued HFD-mediated effects on the bone marrow niche, while transplantation of stools from HFD mice could transfer the effect to normal mice. These findings show that metabolic stress affects the bone marrow niche by alterations of gut microbiota and osteoblast-adipocyte homeostasis.
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Guang-Liang
authors.initials: GL
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hannemann
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Natacha
authors.initials: N
authors.lastname: Ipseiz
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krönke
authors.affiliation: Department of Radiology, Preclinical Imaging, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Luis
authors.initials: L
authors.lastname: Munos
authors.affiliation: Department of Internal Medicine 1, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirtz
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany. Electronic address: georg.schett@uk-erlangen.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen 91054, Germany. Electronic address: aline.bozec@uk-erlangen.de.
authors.forename: Aline
authors.initials: A
authors.lastname: Bozec
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism / Q000382:microbiology; D064307:Microbiota; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D055153:Stem Cell Niche; D013312:Stress, Physiological