title: Mechanism of folate deficiency-induced apoptosis in mouse embryonic stem cells: Cell cycle arrest/apoptosis in G1/G0 mediated by microRNA-302a and tumor suppressor gene Lats2.
abstract: Deficiencies in maternal diet, such as inadequate intake of folate, can inhibit normal development and lead to developmental defects. MicroRNAs (miRNAs) may play a role in mediating the effects of folate deficiency in the growing mammalian embryo, although conclusive evidences to support that possibility are not yet available. The goal of the present study was to investigate whether and how folate deprivation alters the properties of mouse embryonic stem cells (mESCs) in culture. For this purpose, mESCs were cultured in folate-deficient or complete culture medium. The results show that folate-deficient mESCs have a significantly higher rate of apoptosis, accumulate in G0/G1 and fail to proliferate. Expression profiling revealed several miRs and many mRNAs are differently expressed in folate-deficient cells. RT-PCR data confirmed differential expressions of 12 miRNAs in folate-deficient cells. Furthermore, bioinformatics analyses and in vitro studies suggested that miR-302a plays a critical role in mediating the effects of folate on cell proliferation and cell cycle-specific apoptosis by targeting Lats2 gene. Together, these results suggest that the effects of folate deficiency on mammalian development may be mediated by miRNAs that regulate proliferation and/or cell cycle progression in ESCs.
authors: Department of Biochemistry, Peking University Capital Institute of Pediatrics Teaching Hospital, Beijing 100020, China. sarah860113@126.com
authors: Yan
authors: Y
authors: Liang
authors: Yuanyuan
authors: Y
authors: Li
authors: Zhengli
authors: Z
authors: Li
authors: Zhuo
authors: Z
authors: Liu
authors: Zhiping
authors: Z
authors: Zhang
authors: Shaoyan
authors: S
authors: Chang
authors: Jianxin
authors: J
authors: Wu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005494:Folic Acid Deficiency / Q000235:genetics / Q000473:pathology*; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000235:genetics; D017930:Genes, Reporter; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D003470:Culture Media; C558265:MIRN302 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D008156:Luciferases; C522633:LATS2 protein, mouse; D017346:Protein Serine-Threonine Kinases