title: Induction of EMT-like response by BMP4 via up-regulation of lysyl oxidase is required for adipocyte lineage commitment.
abstract: The developmental pathway that gives rise to mature adipocytes involves commitment and terminal differentiation. Our previous findings indicate that BMP4 (bone morphogenetic protein 4) induces nearly complete commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage and knockdown of lysyl oxidase (Lox) disrupts this commitment process. Here, we found that an epithelial-mesenchymal transition (EMT)-like response is required for adipocyte lineage commitment and that Lox is indispensable for this process. When C3H10T1/2 cells were treated with BMP4, Vim and Cdh2 showed up-regulated expression while Cdh1 and Ocln were down-regulated along with enhanced cell migration, which are EMT-like responses. Silencing of Lox in BMP4-treated C3H10T1/2 cells induced a mesenchymal-epithelial transition (MET)-like response associated with the repression of mesenchymal markers, induction of epithelial markers and decreased cell migration. Importantly, blocking the EMT-like response by knocking down Cdh2 or over-expression of Cdh1 impairs adipocyte lineage commitment. EMT is regulated by distinct transcription factors such as Snai1, Snai2 and Twist. In this study, we also found that only Twist was down-regulated after Lox silencing in C3H10T1/2 cells treated with BMP4. This study provides new insights into adipocyte lineage commitment.
authors: Key Laboratory of Molecular Medicine, Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China. haiyanhuang@shmu.edu.cn
authors: Hai-Yan
authors: HY
authors: Huang
authors: Su-Zhen
authors: SZ
authors: Chen
authors: Wen-Ting
authors: WT
authors: Zhang
authors: Shan-Shan
authors: SS
authors: Wang
authors: Yang
authors: Y
authors: Liu
authors: Xi
authors: X
authors: Li
authors: Xia
authors: X
authors: Sun
authors: Yi-Ming
authors: YM
authors: Li
authors: Bo
authors: B
authors: Wen
authors: Qun-Ying
authors: QY
authors: Lei
authors: Qi-Qun
authors: QQ
authors: Tang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D051379:Mice; D062793:Occludin / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism
chemical_list: D055415:Bone Morphogenetic Protein 4; D015820:Cadherins; D062793:Occludin; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C000604429:Snai1 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D008249:Protein-Lysine 6-Oxidase