Zhengjiang Qian (1), Hongchao Li (1), Haiyang Yang (1,2), Qin Yang (1), Zhonghua Lu (1), Liping Wang (1), Ying Chen (3), Xiang Li (1)
Science Advances, 7, Issue 43, October 2021. DOI: 10.1126/sciadv.abi5811x

Abstract

The bone-derived hormone osteocalcin (OCN) is crucial for brain development and neural cognitive functions, yet the exact roles of OCN in central nervous system (CNS) remain elusive. Here, we find that genetic deletion of OCN facilitates oligodendrocyte (OL) differentiation and hypermyelination in the CNS. Although dispensable for the proliferation of oligodendrocyte precursor cells (OPCs), OCN is critical for the myelination of OLs, which affects myelin production and remyelination after demyelinating injury. Genome-wide RNA sequencing analyses reveal that OCN regulates a number of G protein–coupled receptors and myelination-associated transcription factors, of which Myrf might be a key downstream effector in OLs. GPR37 is identified as a previously unknown receptor for OCN, thus regulating OL differentiation and CNS myelination. Overall, these findings suggest that OCN orchestrates the transition between OPCs and myelinating OLs via GPR37 signaling, and hence, the OCN/GPR37 pathway regulates myelin homeostasis in the CNS.

How Our Software Was Used

Dragonfly was used for dataset processing.

Author Affiliation

(1) Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
(2) University of Chinese Academy of Sciences, Beijing 100049, China.
(3) State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China.