Systematic transcriptome profiling of hPSC-derived osteoblasts unveils CORIN's mastery in governing osteogenesis through CEBPD modulation.

Autor:	Zhu D; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Huang MF; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA., Xu A; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Gao X; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Huang YW; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Phan TTT; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Lu L; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA., Chi TY; Department of Materials Science and Engineering, Texas A&M University, College Station, Texas, USA., Dai Y; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Pang LK; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA., Gingold JA; Department of Obstetrics & Gynecology and Women's Health, Einstein/Montefiore Medical Center, Bronx, New York, USA., Tu J; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Huo Z; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Bazer DA; Department of Neurology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA., Shoemaker R; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA., Wang J; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Ambrose CG; Department of Orthopedic Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Shen J; Department of Musculoskeletal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China., Kameoka J; Department of Materials Science and Engineering, Texas A&M University, College Station, Texas, USA; Department of Electrical and Computer Engineering, Texas A&M University, College Station, College Station, Texas, USA., Zhao Z; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Wang LL; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA., Zhang Y; College of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong, China. Electronic address: zhangyang07@hit.edu.cn., Zhao R; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: ruiying.zhao@uth.tmc.edu., Lee DF; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: dung-fang.lee@uth.tmc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Aug; Vol. 300 (8), pp. 107494. Date of Electronic Publication: 2024 Jun 24.
DOI:	10.1016/j.jbc.2024.107494
Abstrakt:	The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect human pluripotent stem cell-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide chromatin immunoprecipitation enrichment and mechanistic studies show that p38 MAPK-mediated CCAAT enhancer binding protein delta (CEBPD) upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in mesenchymal stem cells exerts a negative regulatory effect on osteogenesis through a similar mechanism. Chromatin immunoprecipitation-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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