1919-P: Regulation and Function of Bone Marrow Adipocytes in Osteogenesis and Hematopoiesis

• Published in: Diabetes (New York, N.Y.) Vol. 68; no. Supplement_1
• Main Authors: ZHANG, ZENGDI, HUANG, ZAN, RUAN, HAI-BIN
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2019
• Subjects: Adipocytes; Adipose tissue; Bone marrow; Cell self-renewal; Clonal deletion; Hematopoietic stem cells; Lymphocytes B; Lymphoid cells; N-Acetylglucosamine; Ossification; Osteoblasts; Osteogenesis; Rodents; Stem cell transplantation; Stem cells; Stromal cells
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db19-1919-P

In the bone marrow stroma, skeletal stem cells (SSCs) and their derived stromal cells, osteoblasts and bone marrow adipocytes (BMAs) provide the niche microenvironment to support the self-renewal and differentiation of hematopoietic stem cells (HSCs). However, it’s still largely mysterious how the bone-fat balance is disrupted and whether marrow adiposity contributes to the skewed differentiation of HSCs toward myeloid over lymphoid cells. Here we showed that the O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins determined the adipogenic vs. osteogenic differentiation of SSCs. Conditional deletion of O-GlcNAc transferase (OGT) in Osx1+ cells promoted BMA formation while impaired osteoblast development and bone ossification, which resulted in defective B cell development. To determine the role of BM adipokines in hematopoiesis, we selectively ablated Kit ligand (Kitl) in Osx1+ and Adipoq+ lineages. Both Osx1-Kitl KO and Adipoq-Kitl KO mice lost myeloid progenitors in BM and developed macrocytic anemia. Collectively, our data identified protein O-GlcNAcylation as a novel regulator of SSCs differentiation and demonstrated that BMAs are functionally essential for unperturbed hematopoiesis. Disclosure Z. Zhang: None. Z. Huang: None. H. Ruan: None. Funding National Institutes of Health