成体マウス脂肪組織由来細胞および神経幹細胞からのiPS細胞の効率的な樹立
モナッシュ医学研究所のPaul J Vermaらのグループにより、成体マウス脂肪組織由来細胞および神経幹細胞からのiPS細胞を効率的に樹立したという論文が発表されました。
脂肪組織由来細胞が一番リプログラミング効率良かったとのこと。
Cell Transplant. 2010 Feb 8. [Epub ahead of print]
The efficient generation of induced pluripotent stem (iPS) cells from adult mouse adipose tissue-derived and neural stem cells.
Tat PA, Sumer H, Jones KL, Upton K, Verma PJ.
http://www.ncbi.nlm.nih.gov/pubmed/20144262?dopt=Abstract
Ectopic expression of key reprogramming transgenes in somatic cells enables them to adopt the characteristics of pluripotency. Such cells have been termed induced pluripotent stem (iPS) cells and have revolutionized the field of somatic cell reprogramming as the need for embryonic material is obviated. One of the issues facing both the clinical translation of iPS technology and the efficient derivation of iPS cell lines in the research laboratory is choosing the most appropriate somatic cell type for induction. In this study, we demonstrate the direct reprogramming of a defined population of neural stem cells (NSCs) derived from the sub ventricular zone (SVZ) and adipose tissue derived cells (ADCs) from adult mice using retroviral transduction of the Yamanaka factors: Oct4, Sox2, Klf4 and c-Myc and compared the results obtained with a mouse embryonic fibroblast (mEF) control. We isolated mEFs, NSCs and ADCs from transgenic mice, which possess a GFP transgene under control of the Oct4 promoter and validated GFP expression as an indicator of reprogramming. While transduction efficiencies were not significantly different between the different cell types (mEFs 68.70+/-2.62%, ADCs 70.61+/-15.4%, NSCs, 68.72+/-3%, p=0.97), the number of GFP positive colonies and hence the number of reprogramming events was significantly higher for both NSCs (13.50+/-4.10 colonies, 0.13+/-0.06%) and ADCs (118.20+/-38.28 colonies, 1.14+/-0.77%) when compared with the mEF control (3.17+/-0.29 colonies, 0.03+/-0.005%). ADCs were most amenable to reprogramming with an 8 and 38 fold greater reprogramming efficiency than NSCs and mEFs respectively. Both NSC-iPS and ADC-iPS cells were demonstrated to express markers of pluripotency and could differentiate to the three germ layers both in vitro and in vivo to cells representative of the three germ lineages. Our findings confirm that ADCs are an ideal candidate as a readily accessible somatic cell type for high efficiency establishment of iPS cell lines.