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Reporter 人诱导多能干细胞中的等位基因:发育和疾病的视觉线索。

Reporter Alleles in hiPSCs: Visual Cues on Development and Disease.

机构信息

Laboratory of Cellular Biology, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901 Belo Horizonte, Brazil.

出版信息

Int J Mol Sci. 2024 Oct 13;25(20):11009. doi: 10.3390/ijms252011009.

Abstract

Reporter alleles are essential for advancing research with human induced pluripotent stem cells (hiPSCs), notably in developmental biology and disease modeling. This study investigates the state-of-the-art gene-editing techniques tailored for generating reporter alleles in hiPSCs, emphasizing their effectiveness in investigating cellular dynamics and disease mechanisms. Various methodologies, including the application of CRISPR/Cas9 technology, are discussed for accurately integrating reporter genes into the specific genomic loci. The synthesis of findings from the studies utilizing these reporter alleles reveals insights into developmental processes, genetic disorder modeling, and therapeutic screening, consolidating the existing knowledge. These hiPSC-derived models demonstrate remarkable versatility in replicating human diseases and evaluating drug efficacy, thereby accelerating translational research. Furthermore, this review addresses challenges and future directions in refining the reporter allele design and application to bolster their reliability and relevance in biomedical research. Overall, this investigation offers a comprehensive perspective on the methodologies, applications, and implications of reporter alleles in hiPSC-based studies, underscoring their essential role in advancing both fundamental scientific understanding and clinical practice.

摘要

报告基因等位基因对于推进人类诱导多能干细胞(hiPSC)的研究至关重要,特别是在发育生物学和疾病建模方面。本研究探讨了针对 hiPSC 生成报告基因等位基因的最新基因编辑技术,强调了它们在研究细胞动态和疾病机制方面的有效性。讨论了各种方法,包括 CRISPR/Cas9 技术的应用,用于准确地将报告基因整合到特定的基因组位点中。利用这些报告基因等位基因的研究结果的综合分析揭示了对发育过程、遗传疾病建模和治疗筛选的深入了解,巩固了现有知识。这些 hiPSC 衍生模型在复制人类疾病和评估药物疗效方面表现出了显著的多功能性,从而加速了转化研究。此外,本综述还探讨了改进报告基因等位基因设计和应用的挑战和未来方向,以提高它们在生物医学研究中的可靠性和相关性。总体而言,本研究全面探讨了报告基因等位基因在基于 hiPSC 的研究中的方法、应用和意义,强调了它们在推进基础科学理解和临床实践方面的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b13b/11507014/a668ea9c03d2/ijms-25-11009-g001.jpg

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