Guided differentiation of embryonic stem cells into Pdx1-expressing regional-specific definitive endoderm
Guided differentiation of embryonic stem cells into Pdx1-expressing regional-specific definitive endoderm
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DOI：
10.1634/stemcells.2007-0608
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发表时间：
2008-04-01
期刊：
影响因子：
5.2
通讯作者：
Kume, Shoen
中科院分区：
文献类型：
--
作者：
Shiraki, Nobuaki;Yoshida, Tetsu;Kume, Shoen
从胚胎干细胞（ES）中产生特定的定形内胚层谱系是发育生物学和再生医学中的一个重要问题。这项研究表明，ES细胞被诱导成区域特异性肠内胚层谱系，如胰腺，肝，和其他细胞谱系，当它们直接培养在单层的中胚层来源的支持细胞。详细的时间顺序分析显示，激活素，成纤维细胞生长因子，或骨形态发生蛋白信号在各个步骤是至关重要的，并需要额外的短距离信号分化成Pdx 1表达细胞。在选择性培养条件下，以高效率产生定形内胚层（47%）或Pdx 1阳性胰腺祖细胞（30%）。当移植到肾包膜下时，Pdx 1阳性细胞进一步分化为所有三种胰腺谱系，即内分泌、外分泌和导管细胞。
The generation of specific lineages of the definitive endoderm from embryonic stem (ES) cells is an important issue in developmental biology, as well as in regenerative medicine. This study demonstrates that ES cells are induced sequentially into regional-specific gut endoderm lineages, such as pancreatic, hepatic, and other cell lineages, when they are cultured directly on a monolayer of mesoderm-derived supporting cells. A detailed chronological analysis revealed that Activin, fibroblast growth factor, or bone morphogenetic protein signals are critical at various steps and that additional short-range signals are required for differentiation into Pdx1-expressing cells. Under selective culture conditions, definitive endoderm (47%) or Pdx1-positive pancreatic progenitors (30%) are yielded at a high efficiency. When transplanted under the kidney capsule, the Pdx1-positive cells further differentiated into all three pancreatic lineages, namely endocrine, exocrine, and duct cells.