The role of the transcriptional regulator, Taube nuss, in stem cell function

在整个生命过程中，细胞在许多器官系统中诞生、成熟、衰老、消灭和被新细胞所取代。干细胞是为这种再生过程和修复受损组织而预留的细胞储备。在胚胎发育过程中，瞬态干细胞群存在于组织的生成中。干细胞能够自我更新增殖，能够产生成熟的细胞类型（分化）。如果我们对干细胞的功能有足够的了解，干细胞的再生能力有可能用于治疗帕金森病和肌肉萎缩症等退行性疾病。如果在临床环境中可以影响干细胞的增殖和向成熟细胞类型的分化，则可以鼓励干细胞比正常情况下更有效地取代患病或死亡的细胞。与干细胞可能带来的潜在医疗效益形成鲜明对比的是，我们对控制自我更新和维持广泛分化潜力的分子机制的理解非常有限。我们已经分离出一种新的基因，Taube nuss（-空坚果），它对早期胚胎中第一个瞬时干细胞群体的存活至关重要。在小鼠中，缺乏Taube nuss蛋白会导致这些干细胞死亡，而相同胚胎的分化细胞却能存活。Taube nuss是一种称为转录起始复合物的蛋白质复合体的成员。我们计划研究Taube nuss是否在其他干细胞群中发挥作用。如果是这样的话，我们将不仅能够确定Taube nuss作为干细胞功能的新调节器。我们也将能够证明一种新的调控机制，即参与控制干细胞功能的特定转录起始复合物。

Cells are born, mature, age, are eliminated and replaced by new cells in many organ systems throughout life. Stem cells constitute the reserve of cells set aside for this regeneration process and also for the repair of damaged tissue. During embryonic development transient stem cell populations exist for the generation of tissues. Stem cells are capable of self-renewing proliferation and are able to give rise to mature cell types (differentiation). The regenerative capacity of stem cells could potentially be used in the treatment of degenerative diseases like Parkinson s disease and muscular dystrophy, if we knew enough about their function. If stem cell proliferation and differentiation into mature cell types could be influenced in a clinical setting, stem cells could be encouraged to replace diseased or dead cells more efficiently than they do normally. In sharp contrast to the potential medical benefits that could be derived from stem cells, our understanding of the molecular mechanisms controlling self-renewal and maintenance of a wide differentiation potential are very limited. We have isolated a new gene, Taube nuss (- empty nut), which is essential for the survival of the first transient stem cell population in the early embryo. In mice, lack of Taube nuss protein results in the death of these stem cells, whereas the differentiated cells of the same embryos survive. Taube nuss is a member of a protein complex called transcription initiation complex. We plan to investigate if Taube nuss plays a role in other stem cell populations. If this is the case, we will not only be able to identify Taube nuss as a new regulator of stem cell function. We would also be able to demonstrate a new regulatory mechanism, namely the involvement of specific transcription initiation complexes in the control of stem cell function.