Tian Aiguo, Shi Qing, Jiang Alice, Li Shuangxi, Wang Bing, Jiang Jin
Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.
Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
J Cell Biol. 2015 Mar 16;208(6):807-19. doi: 10.1083/jcb.201409025. Epub 2015 Mar 9.
Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury. The regulatory mechanisms underlying regenerative proliferation are still poorly understood. Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut. Elevated Hh signaling by patched (ptc) mutations drove ISC proliferation noncell autonomously. Inhibition of Hh signaling in the ISC lineage compromised injury-induced ISC proliferation but had little if any effect on homeostatic proliferation. Hh signaling acted in EBs to regulate the production of Upd2, which activated the JAK-STAT pathway to promote ISC proliferation. Furthermore, we show that Hh signaling is stimulated by DSS through the JNK pathway and that inhibition of Hh signaling in EBs prevented DSS-stimulated ISC proliferation. Hence, our study uncovers a JNK-Hh-JAK-STAT signaling axis in the regulation of regenerative stem cell proliferation.
许多成体组织由驻留干细胞维持，这些干细胞会在受到损伤时提高其增殖能力。再生增殖背后的调控机制仍知之甚少。在这里，我们表明损伤会诱导果蝇成虫中肠的成肠细胞（EB）中的Hedgehog（Hh）信号传导，以促进肠道干细胞（ISC）增殖。patched（ptc）突变导致的Hh信号升高非细胞自主地驱动ISC增殖。在ISC谱系中抑制Hh信号传导会损害损伤诱导的ISC增殖，但对稳态增殖几乎没有影响。Hh信号在EB中起作用，以调节Upd2的产生，后者激活JAK-STAT途径以促进ISC增殖。此外，我们表明Hh信号通过JNK途径被葡聚糖硫酸钠（DSS）刺激，并且在EB中抑制Hh信号传导可阻止DSS刺激的ISC增殖。因此，我们的研究揭示了在调节再生干细胞增殖中的JNK-Hh-JAK-STAT信号轴。
