Int. J. Dev. Biol. 54: 1685 - 1695 (2010)
doi: 10.1387/ijdb.103248mb
© UPV/EHU Press

Reprogramming cell fate: a scientific journey from viral enhancers to the master gene regulator Oct4 - an interview with Hans R. Schöler

Michele Boiani*

Max-Planck Institute for Molecular Biomedicine, Münster, Germany

ABSTRACT As science advances, old ideas once considered dogmas are called into question by new observations that reshape our understanding of the biology and evolution of mammals. The fate of embryonic cells has long been considered as sealed, in mammals, at the stage of gastrulation, when the soma (ectoderm, mesoderm, endoderm) and the germ cells segregate from each other owing to the switching on and off of distinct gene expression programs. In this context, the term "reprogramming" means the conversion of a cell's gene expression program, from one characteristic of that cell into one characteristic of a different cell type. Programming and reprogramming rely on orchestras of genes. Dr. Schöler takes us through his scientific journey from his early attempts to clone and study developmentally important genes in viruses, to his discovery of the "master" gene Pou5f1 encoding the transcription factor Oct4. Expression of Pou5f1 marks the cells that belong to the germline - the "metagroup" of cells (including germ cells) that can pass genetic information on to the next generation. Once the germ cells have been set aside and organogenesis has taken place, Oct4 is dispensable in the soma, yet its forced expression elicits a reprogramming process that brings about a pluripotent cell state. To what extent is somatic cell reprogramming dependent on Oct4? Can cells "jump" across the germ layers without Oct4? Can reprogramming ever be perfect if cells do not pass through the germline, which is the natural way of reprogramming genomes through sexual reproduction? These and other burning questions are the topic of this interview with Dr. Schöler.


cell fate, ES cell, Oct4, pluripotency, reprogramming

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