Liang Y.,Peking University |
Liang Y.,Capital Institute of Pediatrics |
Li Y.,Capital Institute of Pediatrics |
Li Z.,Capital Institute of Pediatrics |
And 5 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2012
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. © 2012 Elsevier Ltd.