title: Single transcription factor reprogramming of hair follicle dermal papilla cells to induced pluripotent stem cells.
abstract: Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. However, several issues need to be resolved such as ease, efficiency, and safety of generation of iPS cells. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors and very recently from fibroblasts with Oct4 alone in combination with additional small molecules. Here, we exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after 3 weeks and with efficiencies similar to other cell types reprogrammed with four factors. Dermal papilla-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression, and pluripotency. We conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules.
authors.affiliation: Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Su-Yi
authors.initials: SY
authors.lastname: Tsai
authors.forename: Britta Am
authors.initials: BA
authors.lastname: Bouwman
authors.forename: Yen-Sin
authors.initials: YS
authors.lastname: Ang
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Dung-Fang
authors.initials: DF
authors.lastname: Lee
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
authors.forename: Michael
authors.initials: M
authors.lastname: Rendl
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D016678:Genome; D018392:Genomic Imprinting; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes; D018183:Transplantation Chimera
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011994:Recombinant Proteins