Kim, Ji-Hoon Kang, Jong-Seol Yoo, Kyusang Jeong, Jinguk Park, Inkuk Park, Jong Ho Rhee, Joonwoo Jeon, Shin Jo, Young-Woo Hann, Sang-Hyeon Seo, Minji Moon, Seungtae Um, Soo-Jong Seong, Rho Hyun Kong, Young-Yun 2024-01-19T12:02:23Z 2024-01-19T12:02:23Z 2022-06-09 2022-05 2324-7703 https://pubs.kist.re.kr/handle/201004/115202 The survival of motor neuron (SMN) protein is a major component of the pre-mRNA splicing machinery and is required for RNA metabolism. Although SMN has been considered a fundamental gene for the central nervous system, due to its relationship with neuromuscular diseases, such as spinal muscular atrophy, recent studies have also revealed the requirement of SMN in non-neuronal cells in the peripheral regions. Here, we report that the fibro-adipogenic progenitor subpopulation expressing Dpp4 (Dpp4* FAPs) is required for the neuromuscular system. Furthermore, we also reveal that BRCA1-associated protein-1 (Bap1) is crucial for the stabilization of SMN in FAPs by preventing its ubiquitination-dependent degradation. Inactivation of Bap1 in FAPs decreased SMN levels and accompanied degeneration of the neuromuscular junction, leading to loss of motor neurons and muscle atrophy. Overexpression of the ubiquitination-resistant SMN variant, SMNK186R, in Bap1-null FAPs completely prevented neuromuscular degeneration. In addition, transplantation of Dpp4* FAPs, but not Dpp4??? FAPs, completely rescued neuromuscular defects. Our data reveal the crucial role of Bap1-mediated SMN stabilization in Dpp4* FAPs for the neuromuscular system and provide the possibility of cell-based therapeutics to treat neuromuscular diseases. English AMER SOC CLINICAL INVESTIGATION INC Bap1/SMN axis in Dpp4+ skeletal muscle mesenchymal cells regulates the neuromuscular system Article 10.1172/jci.insight.158380 1 JCI INSIGHT, v.7, no.10 JCI INSIGHT 7 10 Y scie scopus 000802196700001 Medicine, Research & Experimental Research & Experimental Medicine Article SPINAL MUSCULAR-ATROPHY MOTOR-NEURON PROTEIN SKELETAL-MUSCLE SMN PROTEIN NEUROMUSCULAR-JUNCTION MOUSE MODELS FIBRO/ADIPOGENIC PROGENITORS SELECTIVE VULNERABILITY MESENCHYMAL PROGENITOR CELLS CONTRIBUTE