File Download

There are no files associated with this item.

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
Related Researcher

김정범

Kim, Jeong Beom
Molecular Biomedicine Lab.
Read More

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

Differentiation Efficiency of Induced Pluripotent Stem Cells Depends on the Number of Reprogramming Factors

Author(s)
Loehle, MatthiasHermann, AndreasGlass, HannesKempe, AndreaSchwarz, Sigrid C.Kim, Jeong BeomPoulet, ClaireRavens, UrsulaSchwarz, JohannesSchoeler, Hans R.Storch, Alexander
Issued Date
2012-03
DOI
10.1002/stem.1016
URI
https://scholarworks.unist.ac.kr/handle/201301/4286
Fulltext
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84857485529
Citation
STEM CELLS, v.30, no.3, pp.570 - 579
Abstract
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by retroviral overexpression of the transcription factors Oct4, Sox2, Klf4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk for chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC, albeit at lower efficiency. To elucidate the influence of factor reduction on subsequent differentiation, we compared the efficiency of neuronal differentiation in iPSC generated from postnatal murine neural stem cells with either one (Oct4; iPSC(1F-NSC)), two (Oct4, Klf4; iPSC(2F-NSC)), or all four factors (iPSC(4F-NSC)) with those of embryonic stem cells (ESCs) and iPSC produced from fibroblasts with all four factors (iPSC(4F-MEF)). After 2 weeks of coculture with PA6 stromal cells, neuronal differentiation of iPSC(1F-NSC) and iPSC(2F-NSC) was less efficient compared with iPSC(4F-NSC) and ESC, yielding lower proportions of colonies that stained positive for early and late neuronal markers. Electrophysiological analyses after 4 weeks of differentiation identified functional maturity in neurons differentiated from ESC, iPSC(2F-NSC), iPSC(4F-NSC), and iPSC(4F-MEF) but not in those from iPSC(1F-NSC). Similar results were obtained after hematoendothelial differentiation on OP9 bone marrow stromal cells, where factor-reduced iPSC generated lower proportions of colonies with hematoendothelial progenitors than colonies of ESC, iPSC(4F-NSC), and iPSC(4F-MEF). We conclude that a reduction of reprogramming factors does not only reduce reprogramming efficiency but may also worsen subsequent differentiation and hinder future application of iPSC in cell replacement therapies.
Publisher
WILEY-BLACKWELL
ISSN
1066-5099
Keyword (Author)
ReprogrammingStem cellsInduced pluripotent stem cellsNeurogenesisAdult neural stem cells
Keyword
EMBRYONIC STEMHUMAN FIBROBLASTSC-MYCSOMATIC-CELLSGENERATIONINDUCTIONMOUSEOCT4EXPRESSIONDYSPLASIA

qrcode

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.