Genome engineering of stem cell organoids for disease modeling

Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.

ClipR-59 plays a critical role in the regulation of body glucose homeostasis.

By regulating Akt membrane compartmentalization, ClipR-59 modulates adipocyte glucose transport. To elucidate the role of ClipR-59 in the regulation of whole body glucose homeostasis, we have generated adipose tissue specific transgenic mice and examined how forcing expression of ClipR-59 in adipose tissue affects body glucose homeostasis. We found that ClipR-59 adipose transgenic mice showed lower blood glucose level with increased glucose tolerance and enhanced insulin sensitivity. Moreover, ClipR-59 adipose transgenic mice were lean with reduced fat mass and against diet induced obesity. Finally, we examined the potential impact of ClipR-59 on adipose endocrine function and found that ClipR-59 expression enhanced adiponectin secretion in both 3T3-L1 adipocytes and adipose tissue, accompanied with increased circulating adiponectin and enhanced AMPKα phosphorylation at Thr172 in adipose tissue and skeletal muscle. Overall, these studies demonstrate that ClipR-59 is likely an important regulator of body glucose homeostasis and adipocyte function.