Huang Yi-Ting, Hesting Lauren L, Calvi Brian R
Department of Biology, Simon Cancer Center, Indiana University, Bloomington, IN 47405.
bioRxiv. 2024 Mar 14:2024.03.14.585098. doi: 10.1101/2024.03.14.585098.
A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the wing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.
向G/S内周期的程序性发育转换通过细胞大小的增加导致组织生长。非计划的、诱导性内循环细胞（iECs）促进伤口愈合，但也与癌症有关。然而，关于这些iECs如何影响组织生长，仍有许多未知之处。以翅盘为模型，我们发现iECs群体最初会增大，但随后会经历异质性停滞，导致严重的组织生长不足。iECs获得了DNA损伤并激活了Jun N端激酶（JNK）途径，但与其他应激细胞不同，它们具有抗凋亡能力，不会从上皮中清除。相反，iECs进入了一种依赖JNK的可逆性衰老样停滞状态。衰老的iECs促进了二倍体邻近细胞的分裂，但这种代偿性增殖并不能挽救组织生长。我们的研究揭示了iECs的独特特性及其对组织生长的影响，这对于理解它们在伤口愈合和癌症中的作用具有重要意义。
