Oviedo Néstor J, Levin Michael
Center for Regenerative and Developmental Biology, Forsyth Institute, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Development. 2007 Sep;134(17):3121-31. doi: 10.1242/dev.006635. Epub 2007 Aug 1.
The largely unknown mechanisms that regulate adult stem cells probably involve signals from neighboring differentiated cells. Gap junction channels providing direct cell-cell communication via small molecules are a crucial component of morphogenesis and normal physiology. However, no specific gap junction protein has yet been functionally linked to adult/somatic stem cell behavior in vivo or to organ regeneration. We report the identification and characterization of smedinx-11--an innexin gap junction channel gene expressed in the adult stem cells (neoblasts) of the planarian Schmidtea mediterranea. smedinx-11 RNAi treatment inhibits regeneration and abrogates neoblast maintenance. Moreover, smedinx-11 expression is enriched in an irradiation-sensitive subpopulation (;X2') and is required for proper expression of other stem cell-specific markers. Analyses of the smedinx-11 downregulation phenotype revealed a striking anterior-posterior neoblast gradient. Our data demonstrate a novel role for gap junction proteins and suggest gap junction-mediated signaling as a new and tractable control point for adult, somatic stem cell regulation.
调节成体干细胞的机制大多未知,可能涉及来自相邻分化细胞的信号。间隙连接通道通过小分子提供直接的细胞间通讯,是形态发生和正常生理的关键组成部分。然而,尚未有特定的间隙连接蛋白在功能上与体内成体/体细胞干细胞行为或器官再生相关联。我们报告了smedinx-11的鉴定和表征,smedinx-11是一种在涡虫Schmidtea mediterranea的成体干细胞(新生细胞)中表达的连接蛋白间隙连接通道基因。smedinx-11 RNAi处理会抑制再生并消除新生细胞的维持。此外,smedinx-11表达在对辐射敏感的亚群(;X2')中富集,并且是其他干细胞特异性标志物正确表达所必需的。对smedinx-11下调表型的分析揭示了明显的前后新生细胞梯度。我们的数据证明了间隙连接蛋白的新作用,并表明间隙连接介导的信号传导是成体、体细胞干细胞调节的一个新的且易于处理的控制点。