Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes.
Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes.
复制标题
DOI：
10.1016/j.devcel.2009.01.012
复制
发表时间：
2009-03
影响因子：
11.8
通讯作者：
Chan, Lawrence
中科院分区：
文献类型：
--
作者：
Yechoor, Vijay;Liu, Victoria;Espiritu, Christie;Paul, Antoni;Oka, Kazuhiro;Kojima, Hideto;Chan, Lawrence
转录因子Neurogenin3(Ngn3)是胰岛细胞类型指定所必需的。在这里，我们发现，肝脏基因转移的Ngn3短暂地诱导终末分化的肝细胞中的胰岛素，但不能使它们转分化，即将它们的谱系转换为胰岛细胞。然而，由于门脉周围胰岛样细胞团的出现，Ngn3导致小鼠长期糖尿病逆转。这些新的胰岛显示受血糖调节的胰岛素、β细胞特异的转录本和胰岛特异的转录级联，并产生所有四种主要的胰岛激素。它们似乎起源于肝祖细胞，最有可能是内胚层来源的椭圆形细胞。因此，转移单一的谱系定义转录因子Ngn3足以在这些祖细胞中诱导细胞谱系从肝脏向胰岛谱系的转换，这一过程与反式决定一致，即在谱系决定的但不是终末分化的细胞中进行谱系转换。这种体内诱导感受性祖细胞反式决定的范例可能普遍适用于包括糖尿病在内的多种疾病的治疗性器官发生。
The transcription factor Neurogenin3 (Ngn3) is required for islet-cell type specification. Here, we show that hepatic gene transfer of Ngn3 transiently induces insulin in terminally-differentiated hepatocytes but fails to transdifferentiate them, i.e. switch their lineage into islet cells. However, Ngn3 leads to long-term diabetes reversal in mice due to the emergence of periportal islet-like cell clusters. These neo-islets display glycemia-regulated insulin, β-cell-specific transcripts, and an islet-specific transcription cascade, and produce all four major islet hormones. They appear to arise from hepatic progenitor cells, most likely endoderm-derived oval cells. Thus, transfer of a single lineage-defining transcription factor, Ngn3, is sufficient to induce cell-lineage switching from hepatic to an islet lineage in these progenitor cells, a process consistent with transdetermination, i.e, lineage switching in lineage-determined, but not terminally-differentiated cells. This paradigm of induced transdetermination of receptive progenitor cells in vivo may be generally applicable to therapeutic organogenesis for multiple diseases including diabetes.
登录
查看更多内容
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
8.2
作者：
Gao, R;Ustinov, J;Otonkoski, T
通讯作者：
Otonkoski, T
DOI：
10.1152/ajpendo.00321.2002
发表时间：
2003-01-01
影响因子：
5.1
作者：
Hara, M;Wang, XY;Bell, GI
通讯作者：
Bell, GI
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
3.5
作者：
Brun, Thierry;He, Kai Hui Hu;Gauthier, Benoit R.
通讯作者：
Gauthier, Benoit R.