转录因子驱动的人诱导多能干细胞神经元分化用于疾病建模和药物筛选的优化。

IF 4.5 3区 医学 Q2 CELL & TISSUE ENGINEERING
Stem Cell Reviews and Reports Pub Date : 2025-04-01 Epub Date: 2025-01-31 DOI:10.1007/s12015-025-10845-4
Martina Servetti, Martino Caramia, Giulia Parodi, Fabrizio Loiacono, Ennio Nano, Giorgia Biddau, Lorenzo Ferrando, Lisastella Morinelli, Pierluigi Valente, Sergio Martinoia, Andrea Escelsior, Gianluca Serafini, Serena Tamburro, Simona Baldassari, Anna Fassio, Fabio Benfenati, Anna Corradi, Bruno Sterlini
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引用次数: 0

摘要

人脑体外模型的进展是神经病学和精神病学研究的基石,解决了动物模型中物种特异性差异所带来的局限性。利用转录因子重编程方案从诱导多能干细胞(iPSCs)生成人类神经元已被证明可以减少异质性并提高不同干细胞系之间的一致性。尽管取得了显著的进步,但目前的协议仍然存在一些缺点。本研究的重点是标准化和优化通过诱导过表达Neurogenin-2生成ipsc衍生的谷氨酸能神经元的程序。值得注意的改进包括严格审查成纤维细胞重编程后的基因组重排,选择均匀整合的ngn2盒群,以及在神经元分化过程中纳入中间步骤以存储神经元祖细胞。单细胞和网络电生理记录显示,神经培养显示出高度的神经元成熟和一致性。这些进步旨在为神经系统疾病的疾病建模和药物筛选提供更可靠的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening.

Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings. This study focuses on standardizing and optimizing the procedure for iPSC-derived glutamatergic neurons generation through the inducible overexpression of Neurogenin-2. Noteworthy refinements include stringent scrutiny of genomic rearrangements post-fibroblast reprogramming, selection of a homogeneously integrated NGN2-cassettes population, and the incorporation of an intermediate step during neuronal differentiation to store neuronal progenitors. The neural culture showed a high degree of neuronal maturation and consistency, as shown by single-cell and network electrophysiological recordings. These advancements aim to provide more reliable tools for disease modelling and drug screening in neurological disorders.

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来源期刊
Stem Cell Reviews and Reports
Stem Cell Reviews and Reports 医学-细胞生物学
CiteScore
9.30
自引率
4.20%
发文量
0
审稿时长
3 months
期刊介绍: The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.
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