Direct Conversion of Adipocyte Progenitors into Functional Neurons

Abstract

Abstract

Ectopic expression of a set of transcription factors in somatic cells could reprogram the differentiated cell fate into the pluripotent state, and the resultant so-called induced pluripotent stem cells (iPSCs) have been proposed as seed cells for cell therapy–based regenerative medicine. However, their tumorigenicity limited the further application of iPSCs clinically. More recently, collected evidence has shown that differentiated somatic cells could be directly converted into other types of somatic cells through overexpression of transcription factors enriched in the targeted cell types. Induced neurons have been recently converted from fibroblasts; however, it remains unknown if other cell types could be used for neuron induction. One easily accessible cell type, adipocyte progenitor cells (APCs), has the advantage of steady proliferation in vitro and lower mortality rate. In the present study, we demonstrated that APCs could also be converted into functional neurons using the three transcriptional factors (Ascl1, Brn2, Myt1l) that could convert fibroblasts into neurons. Moreover, we also demonstrated that vitamin C could elevate the efficiency of conversion of the APCs and fibroblasts into neurons. The converted cells represent another appropriate cell resource for clinical application and disease modeling.