Specification, maintenance and elimination of stem cell progenitors for the mammalian anteroposterior axis

在胚胎发育期间，脊髓、脊柱和肌肉由干细胞奠定。我们已经表明，这些干细胞是独特的几个原因。与胚胎干细胞（ES）不同，它可以制造身体中的任何组织，或者神经干细胞，只制造神经组织，这些“神经中胚层”或“NM”祖细胞制造两种非常不同的胚胎组织类型，神经管（然后产生脊髓）和中胚层（制造肌肉，骨骼和软骨）。这些干细胞在发育过程中很早就出生了，并且一直活跃到脊髓和脊柱的前体被放下。然后将它们从胚胎中完全取出。如果我们能在培养皿中培养这些细胞，它们将成为分化的肌肉、骨骼和脊髓的有用来源。事实上，与ES细胞不同，NM祖细胞在注射到成年小鼠中时不会产生恶性肿瘤。最近，我们在细胞培养中产生了NM祖细胞样细胞，我们计划研究这些细胞是如何产生的，它们如何形成神经管和中胚层细胞类型，以及胚胎如何知道何时消除它们。一些人类出生异常，包括尾部退化综合征，糖尿病母亲的高风险，可能会出现，因为NM祖细胞没有正确消除，我们将使用我们的知识NM祖细胞在胚胎中研究是否是这种情况。因此，该计划将胚胎细胞的研究与培养细胞相结合，以了解发育和疾病，并产生可能在未来用于细胞治疗的细胞类型。

During embryo development, the spinal cord, vertebral column and muscles are laid down by stem cells. We have shown that these stem cells are unique for several reasons. Unlike embryonic stem (ES) cells, which can make any tissue in the body, or neural stem cells, which only make nervous tissue, these 'neuromesodermal' or 'NM' progenitors make two very distinct embryonic tissue types, the neural tube (which then generates spinal cord) and the mesoderm (which makes muscle, bone and cartilage). These stem cells are born very early during development and are active until the precursors of spinal cord and vertebral column are laid down. They then are completely removed from the embryo. These cells would be a useful source of differentiated muscle, bone, and spinal cord if we could grow them in a culture dish. In fact, unlike ES cells, NM progenitors do not make malignant tumours when injected in adult mice. Recently, we have generated, in cell culture, NM progenitor-like cells and we plan to study how these cells are generated, how they make neural tube and mesodermal cell types, and how the embryo knows when to eliminate them. Several human birth abnormalities including caudal regression syndrome, a high risk for diabetic mothers, may arise because NM progenitors are not correctly eliminated, and we will use our knowledge of NM progenitors in the embryo to study whether this is the case. This programme therefore combines study of cells in embryos with cells in culture to understand development and disease, and to produce cell types that may be useful in the future for cell therapies.