Small molecule and cell contact-inducible systems for controlling expression and differentiation in mouse embryonic stem cells.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2025-05-16 DOI:10.1242/dev.204505
Sarah S Soliman, Devan H Shah, Hana El-Samad, Zara Y Weinberg
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引用次数: 0

Abstract

Synthetic developmental biology uses engineering approaches to understand multicellularity with goals ranging from recapitulating development to building synthetic organisms. Current approaches include engineering multicellular patterning, controlling differentiation, and implementing cooperative cellular behaviors in model systems. Synthetic biology enables these pursuits by providing tools to control cell behavior. Mouse embryonic stem cells (mESCs) offer a well-studied and genetically tractable pluripotent model for pursuing synthetic development questions. However, there is minimal characterization of existing synthetic biology tools in mESCs. Here, we characterize three small molecule and two cell contact-inducible systems for gene expression in and differentiation of mESCs. We show that small molecule and cell-contact inducible systems work reliably and efficiently for controlling expression of arbitrary genetic payloads. We identify how these systems function differently across model differentiations. Furthermore, we show that these systems can drive direct differentiation of mESCs into neurons. Each of these systems can be used on their own or in combination, opening many possibilities for studying developmental principles with high precision.

控制小鼠胚胎干细胞表达和分化的小分子和细胞接触诱导系统。
合成发育生物学使用工程方法来理解多细胞生物,其目标从概括发育到构建合成生物。目前的方法包括设计多细胞模式,控制分化,以及在模型系统中实现协同细胞行为。合成生物学通过提供控制细胞行为的工具来实现这些追求。小鼠胚胎干细胞(mESCs)为研究合成发育问题提供了一个经过充分研究和遗传可处理的多能模型。然而,对mESCs中现有合成生物学工具的描述很少。在这里,我们描述了三种小分子和两种细胞接触诱导系统在mESCs中的基因表达和分化。我们表明,小分子和细胞接触诱导系统可靠而有效地控制任意遗传有效载荷的表达。我们确定这些系统如何在不同的模型差异中发挥不同的作用。此外,我们表明这些系统可以驱动mESCs直接分化为神经元。这些系统中的每一个都可以单独使用或组合使用,为高精度研究发展原理提供了许多可能性。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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