Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo.
Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo.
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DOI：
10.1016/j.stemcr.2013.12.012
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发表时间：
2014-02-11
影响因子：
5.9
通讯作者：
Shivdasani, Ramesh A.
中科院分区：
文献类型：
--
作者：
Roman, Adrianna K. San;Jayewickreme, Chenura D.;Murtaugh, L. Charles;Shivdasani, Ramesh A.
Wnt信号是肠干细胞生态位的一个重要方面，是隐窝细胞增殖和分化所需的。潘氏细胞或上皮下肌成纤维细胞是所需Wnt配体的主要候选来源，但尚未在体内进行测试。为了消除Wnt-配体分泌，我们使用豪猪（Porcn）条件无效小鼠与在上皮中表达诱导型Cre重组酶的菌株杂交，包括Paneth细胞（Villin-CreERT 2）;平滑肌中，包括上皮下肌成纤维细胞（Myh 11-CreERT 2）;并同时在两个隔室中。从任何这些隔室中消除Wnt分泌不会破坏组织形态、细胞增殖、分化或Wnt途径活性。因此，从这些细胞群的Wnt-配体分泌是肠道内稳态，揭示了一个小的细胞类型或显着的和意想不到的冗余是负责生理Wnt信号在体内。在候选的肠小生境细胞中的Porcn敲除消除了体内Wnt分泌来自潘氏细胞或肠上皮下肌成纤维细胞的Wnt是不稳定的生理性肠Wnt信号传导比目前的观点更复杂，认为Wnt信号传导在肠干细胞小生境中是至关重要的，但是产生必需的Wnt配体的细胞类型是未知的。Shivdasani及其同事使用Porcn条件无效小鼠，消除了肠上皮（包括Paneth细胞）、平滑肌（包括上皮下肌成纤维细胞）和两个隔室中的Wnt配体分泌。他们没有发现肠道内稳态或Wnt信号的缺陷，揭示了意想不到的生态位冗余或复杂性。
Wnt signaling is a crucial aspect of the intestinal stem cell niche required for crypt cell proliferation and differentiation. Paneth cells or subepithelial myofibroblasts are leading candidate sources of the required Wnt ligands, but this has not been tested in vivo. To abolish Wnt-ligand secretion, we used Porcupine (Porcn) conditional-null mice crossed to strains expressing inducible Cre recombinase in the epithelium, including Paneth cells (Villin-CreERT2); in smooth muscle, including subepithelial myofibroblasts (Myh11-CreERT2); and simultaneously in both compartments. Elimination of Wnt secretion from any of these compartments did not disrupt tissue morphology, cell proliferation, differentiation, or Wnt pathway activity. Thus, Wnt-ligand secretion from these cell populations is dispensable for intestinal homeostasis, revealing that a minor cell type or significant and unexpected redundancy is responsible for physiologic Wnt signaling in vivo. Porcn knockout in candidate intestinal niche cells eliminates Wnt secretion in vivo Wnts from Paneth cells or intestinal subepithelial myofibroblasts are dispensable Physiologic intestinal Wnt signaling is more complex than current views suggest Wnt signaling is crucial in the intestinal stem cell niche, but the cell types producing essential Wnt ligands are unknown. Using Porcn conditional-null mice, Shivdasani and colleagues eliminated Wnt ligand secretion from intestinal epithelium, including Paneth cells; smooth muscle, including subepithelial myofibroblasts; and in both compartments. They found no defects in intestinal homeostasis or Wnt signaling, revealing unanticipated niche redundancy or complexity.
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影响因子：
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作者：
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影响因子：
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