Nanog is the gateway to the pluripotent ground state (Cell, 2009, 138:722-737)

報告日期: 2009/12/15
報告時間: 17:05/17:55
報告學生: 林秀冠
講評老師: 莫凡毅

Nanog is the gateway to the pluripotent ground state

Cell 138, 722–737, August 21, 2009


Speaker : Hsiu-Kuan Lin (林秀冠)

Commentator : Fan-E Mo (莫凡毅 老師)

Date : 2009-12-15

Room : 602



Pluriotency means the capacity of a single cell to generate all cell lineages flexibly during organism development. Naturally, pluripotency is generated during mammalian development through formation of the epiblast. Thus, the pluripotent embryonic stem cells could be established from immortalized naive early epiblast cells. Accumulated studies showed that pluripotent cells could also be created by reprogramming somatic cells, either by fusion with pre-existing pluripotent cells or by transfection with regulatory transcription factors. However, how pluripotent cells are generated remains unclear. Nanog is a highly divergent homeodomain protein and is expressed in pluripotent embryo cells, derivative embryonic stem (ES) cells and developing germline. Evidence showed that Nanog does facilitate molecular reprogramming and promote the transfer of pluripotency after ES cell fusion in human cells. In this study, authors tried to clarify the role of Nanog in generation or maintenance of pluripotency. They demonstrated Nanog dosage was critical for cell fusion-induced reprogramming. Nanog was no longer necessary in iPS cells once pluripotency had been attained by reprogramming but specifically required for partially reprogrammed pre-iPS to reach ground state pluripotency. Forced expression of Nanog in EpiSC (derived from the epithelilalized epiblast of post-implantation embryos) orchestrated the transition to ground state pluripotency. Using immunostaining, they showed that Nanog uniquely marked the epiblast in the mature blastocyst and was mutually exclusive with expression of the Gata factors, whereas Oct4 is ubiquitous throughout the ICM. Furthermore, Nanog expression was coincident with the domain of X chromosome reactivation. Finally, they demonstrate that Nanog null ICM cells were unable to progress into a correctly specified and viable epiblast and that hypoblast either did not form or rapidly degenerate. Nanog null ICM cells were blocked in a transition stage of ICM development. In conclusion, these findings suggest that Nanog lies at the heart of a convergent mechanism for attaining the ground state of authentic pluripotency both in embryonic development and in the final phase of somatic cell reprogramming.


References :

1.  Mitsui, K., (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and EScells. Cell 113, 631–642.