Cell Stem Cell：Oct4蛋白不具有调节成体干细胞作用
美国科学家近日通过在小鼠干细胞中的实验，对蛋白Oct4作为成体干细胞标记物的有效性提出了挑战，认为Oct4并不具有调节成体干细胞的作用。相关论文10月11日发表在《细胞－干细胞》上。
Oct4蛋白能使胚胎干细胞维持在一个多能性的未分化状态，它控制着胚胎形成早期的基因表达，但随后很快会在体细胞中关闭这一功能。正因如此，很多科学家认为Oct4蛋白在成体干细胞中也应该具有相同的作用。
在最新的研究中，美国怀特海生物医学研究所的Rudolf Jaenisch实验室采用多种方法，测试了小鼠成体干细胞中Oct4的表达，结果全部得到了否定结果。
荷兰伊拉兹马斯医学中心的病理学家Leendert Looijenga表示，此次研究并没有否定成体干细胞的多能性，不过它表明了成体干细胞的调节方式与胚胎干细胞的不同。（科学网 梅进/编译）
原始出处:
Cell Stem Cell, Vol 1, 403-415, 11 October 2007
Article
Oct4 Expression Is Not Required for Mouse Somatic Stem Cell Self-Renewal
Christopher J. Lengner,1 Fernando D. Camargo,1 Konrad Hochedlinger,3 G. Grant Welstead,1 Samir Zaidi,2 Sumita Gokhale,1 Hans R. Scholer,4 Alexey Tomilin,5 and Rudolf Jaenisch1,2,
1 Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
3 Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, MA 02114, USA
4 Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany
5 Institute of Cytology, Russian Academy of Science, 4 Tikhoretski Avenue, 194064 St-Petersburg, Russia
Corresponding author
Rudolf Jaenisch
jaenisch@wi.mit.edu
Summary
The Pou domain containing transcription factor Oct4 is a well-established regulator of pluripotency in the inner cell mass of the mammalian blastocyst as well as in embryonic stem cells. While it has been shown that the Oct4 gene is inactivated through a series of epigenetic modifications following implantation, recent studies have detected Oct4 activity in a variety of somatic stem cells and tumor cells. Based on these observations it has been suggested that Oct4 may also function in maintaining self-renewal of somatic stem cells and, in addition, may promote tumor formation. We employed a genetic approach to determine whether Oct4 is important for maintaining pluripotency in the stem cell compartments of several somatic tissues, including the intestinal epithelium, bone marrow (hematopoietic and mesenchymal lineages), hair follicle, brain, and liver. Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal.
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