Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem (iPS) cells from mouse mature adipocytes by forced expression of six transcription factors (Oct4, Sox2, c-Myc, Klf4, Rarγ, and Lrh1) with a piggyBac transposon-based strategy. The resulting iPS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1, and remained pluripotent on a 2i media. In vitro differen- tiation of the iPS cells showed that the cell derivatives of all three germ layers could be readily obtained through forma- tion of embryoid bodies. Most importantly, these adipocyte- derived iPS cells were capable of producing chimera with high frequencies when reintroduced into early-stage em- bryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming tech- nology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.
Prof.Yang Zhengang’s laboratory at the Institutes of Brain Science,Fudan University,reported subcortical origins of human and monkey neocortical interneurons,which was published in Nature Neuroscience(2013,16(11):1588—1597).GABAergic inhibitory interneurons play crucial roles in the development and organization of cortical networks.Nearly all GABAergic neurons in rodent cortex are generated from the ventral telencephalon.
Objective:To investigate the effects of BCNU/PLGA microspheres on tumor growth,apoptosis and chemotherapy resistance in a C57BL/6 mice orthotopic brain glioma model using GL261 cell line.Methods:BCNU/PLGA sustained-release microspheres were prepared by the water-in-oil-in-water emulsion technique.GL261 cells were intracranially injected into C57BL/6 mouse by using the stereotactic technology.A total of 60 tumor-bearing mice were randomly and equally divided into three groups:untreated control,PLGA treated,BCNU/PLGA treated.Magnetic resonance imaging (MRI) was taken to evaluate tumor volume.BCNU/PLGA sustained-release wafers were implanted in the treatment group two weeks after inoculation.Survival time and quality were observed.Specimens were harvested,and immunohistochemical staining was used to check the expression of Bax,Bcl-2,and O6-methylguanine-DNA methyltransferase (MGMT).Statistical methods was used for analysis of relevant data.Results:BCNU/PLGA sustained-release wafers were fabricated and implanted successfully.There is statistical difference of survival time between the BCNU/PLGA treated group and control groups (P<0.05).MRIscan showed inhibitory effect of BCNU/PLGA on tumor growth.Compared to the group A and B,BCNU/PLGA decreased the expression of apoptosis related gene Bcl-2 (P<0.05),but did not elevate the expression level of Bax (P>0.05),with the ratio of Bax/Bcl-2 increased.For MGMT protein expression,no statistically significant change was found in treated group (P>0.05).Conclusions:Local implantation of BCNU/PLGA microspheres improved the survival quality and time of GL261 glioma-bearing mice significandy,inhibited the tumor proliferation,induced more cell apoptosis,and did not increase the chemotherapy resistance.