Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control

Yu, Guiling; Zhang, Mingliang; Gao, Ling; Zhou, Yang; Qiao, Longliang; Yin, Jianli; Wang, Yiwen; Zhou, Jian

doi:10.1016/j.ymthe.2021.09.004

Cited by 13 publications

(19 citation statements)

References 62 publications

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“…More recently, a sophisticated approach to inducing neuronal cell death through light‐controlled transcription of a cytotoxic ion channel was implemented in zebrafish [69]. Light‐controlled transcription has also previously been used to induce insulin translation and expression in vivo by implanting engineered cells in mice [70]. Additionally, multiple optogenetic tools have been developed to control beta cell activity both in vitro and in vivo .…”

Section: Modulating Islet Function In Zebrafishmentioning

confidence: 99%

Microscopic modulation and analysis of islets of Langerhans in living zebrafish larvae

et al. 2022

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Microscopic analysis of molecules and physiology in living cells and systems is a powerful tool in life sciences. While in vivo subcellular microscopic analysis of healthy and diseased human organs remains impossible, zebrafish larvae allow studying pathophysiology of many organs using in vivo microscopy. Here, we review the potential of the larval zebrafish pancreas in the context of islets of Langerhans and Type 1 diabetes. We highlight the match of zebrafish larvae with the expanding toolbox of fluorescent probes that monitor cell identity, fate and/or physiology in real time. Moreover, fast and efficient modulation and localization of fluorescence at a subcellular level, through fluorescence microscopy, including confocal and light sheet (single plane illumination) microscopes tailored to in vivo larval research, is addressed. These developments make the zebrafish larvae an extremely powerful research tool for translational research. We foresee that living larval zebrafish models will replace many cell line‐based studies in understanding the contribution of molecules, organelles and cells to organ pathophysiology in whole organisms.

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Section: Modulating Islet Function In Zebrafishmentioning

confidence: 99%

Microscopic modulation and analysis of islets of Langerhans in living zebrafish larvae

et al. 2022

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“…An integrated system of monitoring and treatment is poised for clinical translation. FRL‐activated human islet‐like designer (FAID) cells have been developed for long‐term blood glucose control [84]. The FRL‐triggered optogenetic device was introduced into human mesenchymal stem cells, encapsulated in poly( L ‐lysine)‐alginate, and implanted subcutaneously under the dorsum of type 1 diabetic mice.…”

Section: Introductionmentioning

confidence: 99%

Engineering of optogenetic devices for biomedical applications in mammalian synthetic biology

Guan

Gao

2022

Engineering Biology

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Gene-and cell-based therapies are the next frontiers in the field of medicine. Both are transformative and innovative therapies; however, a lack of safety data limits the translation of such promising technologies to the clinic. Improving the safety and promoting the clinical translation of these therapies can be achieved by tightly regulating the release and delivery of therapeutic outputs. In recent years, the rapid development of optogenetic technology has provided opportunities to develop precision-controlled gene-and cellbased therapies, in which light is introduced to precisely and spatiotemporally manipulate the behaviour of genes and cells. This review focuses on the development of optogenetic tools and their applications in biomedicine, including photoactivated genome engineering and phototherapy for diabetes and tumours. The prospects and challenges of optogenetic tools for future clinical applications are also discussed.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…BphP1 was used in several OTs for the regulation of transcription ( Kaberniuk et al, 2016 ; Redchuk et al, 2017 , 2018b , 2018a ), intracellular protein targeting ( Redchuk et al, 2017 ; 2018b ; 2018a , 2020 ), and cell signaling control ( Kaberniuk et al, 2016 ; Redchuk et al, 2020 ). Non-invasive control of bacteriophytochome-based OTs was demonstrated in living mice ( Kaberniuk et al, 2016 ; Shao et al, 2017 ; Fomicheva et al, 2019 ; Wu et al, 2020 ; Wang et al, 2021 ; Yu et al, 2022 ). The functionality of light-induced BphP1-QPAS1 interaction was also shown in primary neurons ( Redchuk et al, 2018b ).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Localization Signals for Optimization of Genetically Encoded Tools in Neurons

Karasev

Baloban

Verkhusha

et al. 2022

Front. Cell Dev. Biol.

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Nuclear transport in neurons differs from that in non-neuronal cells. Here we developed a non-opsin optogenetic tool (OT) for the nuclear export of a protein of interest induced by near-infrared (NIR) light. In darkness, nuclear import reverses the OT action. We used this tool for comparative analysis of nuclear transport dynamics mediated by nuclear localization signals (NLSs) with different importin specificities. We found that widely used KPNA2-binding NLSs, such as Myc and SV40, are suboptimal in neurons. We identified uncommon NLSs mediating fast nuclear import and demonstrated that the performance of the OT for nuclear export can be adjusted by varying NLSs. Using these NLSs, we optimized the NIR OT for light-controlled gene expression for lower background and higher contrast in neurons. The selected NLSs binding importins abundant in neurons could improve performance of genetically encoded tools in these cells, including OTs and gene-editing tools.

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Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control

Cited by 13 publications

References 62 publications

Microscopic modulation and analysis of islets of Langerhans in living zebrafish larvae

Microscopic modulation and analysis of islets of Langerhans in living zebrafish larvae

Engineering of optogenetic devices for biomedical applications in mammalian synthetic biology

Nuclear Localization Signals for Optimization of Genetically Encoded Tools in Neurons

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