Activation of neural cell fate programs toward direct conversion of adult human fibroblasts into tri-potent neural progenitors using OCT-4.
Several transcription factors and methods have been used to convert fibroblasts directly to neural fate and have provided insights into molecular mechanisms as to how each of these required factors orchestrate neural fate conversion. Here, we provide evidence and detailed characterization of the direct conversion process of primary adult human fibroblasts (hFib) to neural progenitor cells (NPC) using OCT4 alone. Factors previously associated with neural cell fate conversion were induced during hFib-NPC(OCT-4) generation, where OCT-4 alone was sufficient to induce neural fate conversion without the use of promiscuous small-molecule manipulation. Human Fib-NPC(OCT-4) proliferate, express neural stem/progenitor markers, and possess developmental potential that gives rise to all three major subtypes of neural cells: astrocytes, oligodendrocytes, and neurons with functional capacity. We propose a de-convoluted reprogramming approach for neural fate conversion in which OCT4 is sufficient for inducing neural conversion from hFib for disease modeling as well as the fundamental study of early neural fate induction.
1 Faculty of Health Sciences, Stem Cell and Cancer Research Institute, McMaster University , Hamilton, ON, Canada .
Ryan R
RR
Mitchell
Eva
E
Szabo
Yannick D
YD
Benoit
Daniel T
DT
Case
Rami
R
Mechael
Javier
J
Alamilla
Jong Hee
JH
Lee
Aline
A
Fiebig-Comyn
Deda C
DC
Gillespie
Mickie
M
Bhatia
D000200:Action Potentials; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000209:etiology / Q000473:pathology
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors