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 dis- ease inf...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 dis- ease 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 combi- nation 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.展开更多
A better understanding of the molecular mechanisms that control the UCP1 expression in brown and beige adipocytes is essential for us to modulate adipose cell fate and promote thermogenesis,which may provide a therape...A better understanding of the molecular mechanisms that control the UCP1 expression in brown and beige adipocytes is essential for us to modulate adipose cell fate and promote thermogenesis,which may provide a therapeutic view for the treatment of obesity and obesity-related diseases.To systematically identify cis-element(s)that transcriptionally regulates Ucp1,we here took advantage of the high-throughput CRIPSR-Cas9 screening system,and performed an in situ saturating mutagenesis screen,by using a customized sgRNA library targeting the~20 kb genomic region near Ucp1.Through the screening,we have identified several genomic loci that may contain key regulatory element for Ucp1 expression in cultured brown and white adipocytes in vitro,and in inguinal white adipose tissue in vivo.Our study highlights a broadly useful approach for studying cis-regulatory elements in a high-throughput manner.展开更多
文摘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 dis- ease 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 combi- nation 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.
基金supported by grants from the National Key R&D Program of China(2017YFA0102800,2017YFA0103700)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030402)the National Natural Science Foundation of China(31670829,31971063).
文摘A better understanding of the molecular mechanisms that control the UCP1 expression in brown and beige adipocytes is essential for us to modulate adipose cell fate and promote thermogenesis,which may provide a therapeutic view for the treatment of obesity and obesity-related diseases.To systematically identify cis-element(s)that transcriptionally regulates Ucp1,we here took advantage of the high-throughput CRIPSR-Cas9 screening system,and performed an in situ saturating mutagenesis screen,by using a customized sgRNA library targeting the~20 kb genomic region near Ucp1.Through the screening,we have identified several genomic loci that may contain key regulatory element for Ucp1 expression in cultured brown and white adipocytes in vitro,and in inguinal white adipose tissue in vivo.Our study highlights a broadly useful approach for studying cis-regulatory elements in a high-throughput manner.
