Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons.

Shu-Zhen Zhang,Li-Xiang Ma,Zhong-Feng Wang,Wen-Jing Qian,Hong-Fu Li,Zhi-Ying Wu,Hong-Xia Wang

doi:10.1155/2016/2452985

Abstract

Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.

Highlights

Reprogramming techniques have been used to generate induced pluripotent stem cells from human fibroblasts [1]
Somatic cells have been successfully converted into myoblasts [6], chondrocytes [7], functional cardiomyocytes [8], functional hepatocyte-like cells [9], hepatic stem cells [10], multilineage blood progenitors [11], neural stem cells [12], functional neurons [13,14,15], even more specific neurons such as motor neurons [16], and dopaminergic neurons [17, 18]
We tried the protooncogene Myc, which enhanced the efficiency of induced pluripotent stem cells (iPSCs) generation [25], in combination with the aforementioned 4 factors

Summary

Introduction

Reprogramming techniques have been used to generate induced pluripotent stem cells (iPSCs) from human fibroblasts [1]. Patient-derived iPSCs differentiating into mature cells could be useful tools for disease modeling and cell-based therapy [2]. Reprogrammed cells may serve as potential alternative tools for disease modeling and cell-based therapy. An important milestone in the field of cell lineage conversions was the discovery that the single factor MyoD was sufficient to convert fibroblasts to myoblasts [5]. Somatic cells have been successfully converted into myoblasts [6], chondrocytes [7], functional cardiomyocytes [8], functional hepatocyte-like cells [9], hepatic stem cells [10], multilineage blood progenitors [11], neural stem cells [12], functional neurons [13,14,15], even more specific neurons such as motor neurons [16], and dopaminergic neurons [17, 18]

Methods

Results

Conclusion