Nature Genetics：激活关键分子路径能增加肺干细胞

生物谷报道：美国科学家近日研究发现，激活一个重要的分子路径能够增加肺干细胞。这一发现有助于开发相关治疗方案以进行伤后或病后肺部组织的修复。相关论文发表在《自然—遗传学》（Nature Genetics）上。

美国宾夕法尼亚大学医学院的Edward Morrisey和同事研究发现，激活Wnt信号路径能够增加细支气管肺泡干细胞（bronchioalveolar stem cells）的数量。一种名为GATA6的蛋白能够抑制Wnt路径，方式是通过直接调控Wnt路径中另一种名为Fzd2的蛋白的表达。

Wnt路径是干细胞生物学中一个主要的路径。GATA6负调控Wnt路径并且其已被证明在胚胎干细胞复制和分化中也起重要作用，这表明这两种路径相关联的地方不限于肺干细胞，它们在心脏、肠道以及胰腺等组织中也发挥着重要作用。

Wnt路径可用锂等物质进行药理学调控，应用这些物质可以使肺部或其它组织中的关键干细胞群进行强制性扩张和分化，以对成熟组织进行伤后或病后修复。

Morrisey实验室今后将对Wnt路径对肺部及其它组织中的成熟组织修复进行更广泛的基础性研究，同时也将开始确定对这条路径的药理学激活或抑制是否真的可以用于治疗。（生物谷 www.bioon.com）

生物谷推荐原始出处：

Nature Genetics，doi:10.1038/ng.157，Yuzhen Zhang，Edward E Morrisey

A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration

Yuzhen Zhang¹, Ashley M Goss², Ethan David Cohen¹, Rachel Kadzik², John J Lepore¹, Karthika Muthukumaraswamy¹, Jifu Yang¹, Francesco J DeMayo³, Jeffrey A Whitsett⁴, Michael S Parmacek^1,^5,⁶ & Edward E Morrisey^1,^2,^5,⁶

Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta -catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.