Dear Editor,Homeostasis and repair are critical biological processes that allow for tissue and organ preservation and function in multicellular organisms.Their regulation and extension vary drastically across the animal kingdom,and mammals show limited tissue-specific regenerative capacity that declines with age.During aging,articular cartilage is one of the tissues that undergo substantial changes in the matrix structure,molecular composition,metabolic activity,and mechanical properties(Loeser et al.2016).
Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging rate.Notably,they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high accuracy.This progress en-lightens us in many aspects particularly in applying this novel set of bio-markers on studying the mech-anism of aging rate using adult tissue-specifi c stem cells,building up a potential quantitative model to explore the mechanism for other epigenetic factors like non-coding RNA,and understanding the princi-ple and mechanism of 3D chromatin structure in epigenetic modulation.
Ming LiWensu LiuTingting YuanRuijun BaiGuang-Hui LiuWeizhou ZhangJing Qu
Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.
Tomoaki HishidaEric Vazquez-FerrerYuriko Hishida-NozakiIgnacio Sancho-MartinezYuta TakahashiFumiyuki HatanakaJun WuAlejandro OcampoPradeep ReddyMin-Zu WuLaurie GerkenReuben J. ShawConcepcion Rodriguez EstebanChristopher BennerHiroshi NakagawaPedro Guillen GarciaEstrella Nunez DelicadoAntoni CastellsJosep M. CampistolGuang-Hui LiuJuan Carlos Izpisua Belmonte
