The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. ...The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.展开更多
基金supported by the grants from the National Natural Science Foundation of China (Nos. 31271582 and 31030049)Wenzhou Medical University (No. XNK07005)+2 种基金Research Foundation for Advanced Talents of Wenzhou Medical College (No. QTJ08012)the National Basic Research Program of China (Nos. 2011CB943901, 2011 CB943902 and 2011CB943802)Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDA01010101)
文摘The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.
