Stem cells? Tumor stem cells? Induced stem cells?
Pluripotency? Cell proliferation?
More cell proliferation, more chance get re-programmed?
Exciting!!
"Remarkably, however, Melan A-derived secondary cells gave rise to iPS cells at efficiencies of up to 65%, indicating that immortalization endows almost two in three cells with the potential to form iPS cells"
"We found that MEFs treated with Trp53 shRNA at any time point during reprogramming gave rise to iPS cell colonies at higher efficiency than control cells"
"Because Trp53 and p19Arf are guardians of chromosomal stability, however, their manipulation in a therapeutic setting should be approached with caution. Primary cell populations with low endogenous levels of active Trp53 or p16Ink4a and p19Arf (refs 24–26) or cells with a high endogenous proliferative potential, such as somatic stem and progenitor cells27, might provide an alternative and safer source for producing iPS cells at high efficiency."
Nature. 2009 Aug 9.
Immortalization eliminates a roadblock during cellular reprogramming into iPS cells.
Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K.
[1] Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [3] Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl-University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany [4] These authors contributed equally to this work.
The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells. The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19(Arf) (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf-Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular subpopulations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis.
iPS from progenitors ...
[...] August, there was a paper talking about “how immortality could improve cell reprogramming to pluripotency“. Today, another Boston group presents convincing evidence suggests that the key to [...]