title: The effects of LSD1 inhibition on self-renewal and differentiation of human induced pluripotent stem cells.
abstract: Human induced pluripotent stem cells (hiPSCs) are capable of unlimited self-renewal and can generate nearly all cells in the body. Changes induced by different LSD1 activities on the regulation of hiPSC self-renewal and differentiation and the mechanism underlying such changes were determined. We used two different LSD1 inhibitors (phenelzine sulfate and tranylcypromine) and RNAi technique to inhibit LSD1 activity, and we obtained hiPSCs showing 71.3%, 53.28%, and 31.33% of the LSD1 activity in normal hiPSCs. The cells still maintained satisfactory self-renewal capacity when LSD1 activity was at 71.3%. The growth rate of hiPSCs decreased and cells differentiated when LSD1 activity was at approximately 53.28%. The hiPSCs were mainly arrested in the G0/G1 phase and simultaneously differentiated into endodermal tissue when LSD1 activity was at 31.33%. Teratoma experiments showed that the downregulation of LSD1 resulted in low teratoma volume. When LSD1 activity was below 50%, pluripotency of hiPSCs was impaired, and the teratomas mainly comprised endodermal and mesodermal tissues. This phenomenon was achieved by regulating the critical balance between histone methylation and demethylation at regulatory regions of several key pluripotent and developmental genes.
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Nevada Cancer Institute, Las Vegas, NV 89135, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Deng
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Cell Therapy Public Service Platform, Shenzhen 518020, China. Electronic address: frli62@163.com.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Li
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D000066673:Cell Self Renewal; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008745:Methylation; D010624:Phenelzine / Q000494:pharmacology; D034622:RNA Interference; D014191:Tranylcypromine / Q000494:pharmacology
chemical_list: D006657:Histones; D014191:Tranylcypromine; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010624:Phenelzine
keywords: Differentiation; LSD1; Mechanism; Self-renewal; hiPSCs