category
bioRxiv
date
Mar 24, 2026
slug
status
Published
summary
开发了具有抗沉默能力的双着陆垫胚胎干细胞(KELPE),支持多转基因稳定整合;优化了合成邻标技术(PUFFFIN);设计了新型synNotch接收器细胞,实现可控的细胞间通讯和编程细胞死亡。
tags
基因编辑
合成生物学
type
Post
📄 原文题目
KELPE: knock-in exchangeable dual landing pad embryonic stem cells enable efficient screening of synthetic gene circuits
🔗 原文链接
💡 AI 核心解读
开发了具有抗沉默能力的双着陆垫胚胎干细胞(KELPE),支持多转基因稳定整合;优化了合成邻标技术(PUFFFIN);设计了新型synNotch接收器细胞,实现可控的细胞间通讯和编程细胞死亡。
📝 英文原版摘要
The establishment of genetic circuits in pluripotent stem cells (PSCs) allows to model and manipulate developmental events. However, prototyping complex circuitry remains challenging, due to limitations in screening circuit components and transgene silencing. Here, we introduce KELPE: PSCs with two silencing-resistant insulated genomic landing pads targeted to genomic safe harbour sites. KELPE cells enable the stable integration of multiple transgenes into the same genomic region, facilitating fair comparisons of genetic circuit components. We demonstrate this by fine-tuning "synthetic neighbour-labelling" technologies. We first generate optimised PUFFFIN PSCs, which report on cell-cell interactions by fluorescently labelling wild-type neighbours. We then generate new synNotch "receiver" PSCs, which can trigger expression of any transgene following interaction with a synthetic ligand presented by "sender" cells of interest. We describe an optimised circuit syntax that abolishes ligand-independent transgene induction in receiver PSCs, and showcase this by synthetically programming cell death in receiver cells engineered to express a toxin following interaction with sender cells. In summary, we describe a new cell line that facilitates silencing-resistant transgene expression and prototyping of synthetic biology tools in a developmentally-relevant model.
- 作者:NotionNext
- 链接:https://tangly1024.com/article/32d48bd6-1f96-818d-b9da-d4cc1e11b0e7
- 声明:本文采用 CC BY-NC-SA 4.0 许可协议,转载请注明出处。
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