Direct reprogramming of Huntington's disease patient fibroblasts into neuron-like cells leads to abnormal neurite outgrowth, increased cell death, and aggregate formation.

ABSTRACT: Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington's disease (HD) patient fibroblasts into neurons by modulation of cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neur

SUBMITTER: Liu Y 

PROVIDER: S-EPMC4183653 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature