近日，國際學術期刊cell reports在線發表了美國科學家的一項最新研究進展，他們發現在小腸幹細胞和小腸穩態調節過程中，Notch和Wnt信號扮演了重要調控作用，阻斷Notch信號會引起小腸幹細胞分化失衡，並且在這一過程中伴隨對Wnt信號途徑的抑製解除。

        器官的穩態平衡需要對成體幹細胞進行嚴格調控，並通過多種信號整合實現幹細胞向終末細胞的分化過程。在小鼠的小腸中，Notch和wnt信號對於小腸幹細胞維持以及腸道負責消化液分泌的細胞和負責營養吸收的細胞之間的分化平衡都是非常必要的。

        研究人員發現當Notch信號受到抑製，小腸幹細胞傾向於向分泌細胞方向分化，而影響營養吸收細胞的分化過程。研究人員利用具有功能阻斷特性的抗體特異性阻斷Notch受體，結果發現阻斷Notch信號會解除對Wnt信號途徑的抑製作用，擾亂小腸幹細胞的正常功能，導致促分泌功能相關基因的錯誤表達。同時，研究人員還發現抑製wnt信號通路能夠恢複因Notch信號阻斷所造成的表型。

        這項研究闡述了一種維持幹細胞活性以及分化平衡的負向調節機製，並且還證明了Wnt與Notch信號之間的相互作用對與維持成體幹細胞的正常功能具有重要意義。(生物穀Bioon.com)

        DOI: http://dx.doi.org/10.1016/j.celrep.2015.03.007

        Opposing Activities of Notch and Wnt Signaling Regulate Intestinal Stem Cells and Gut Homeostasis

        Hua Tian5, Brian Biehs5, Cecilia Chiu, Christian W. Siebel, Yan Wu, Mike Costa, Frederic J. de Sauvagecorrespondenceemail, Ophir D. Klein

        Proper organ homeostasis requires tight control of adult stem cells and differentiation through the integration of multiple inputs. In the mouse small intestine, Notch and Wnt signaling are required both for stem cell maintenance and for a proper balance of differentiation between secretory and absorptive cell lineages. In the absence of Notch signaling, stem cells preferentially generate secretory cells at the expense of absorptive cells. Here, we use function-blocking antibodies against Notch receptors to demonstrate that Notch blockade perturbs intestinal stem cell function by causing a derepression of the Wnt signaling pathway, leading to misexpression of prosecretory genes. Importantly, attenuation of the Wnt pathway rescued the phenotype associated with Notch blockade. These studies bring to light a negative regulatory mechanism that maintains stem cell activity and balanced differentiation, and we propose that the interaction between Wnt and Notch signaling described here represents a common theme in adult stem cell biology.