Transcription factors and splice factors - interconnected regulators of stem cell differentiation.

IF 2.3 Q4 CELL & TISSUE ENGINEERING Current Stem Cell Reports Pub Date : 2023-06-01 Epub Date: 2023-06-29 DOI:10.1007/s40778-023-00227-2
Madison M Mehlferber, Muge Kuyumcu-Martinez, Clint L Miller, Gloria M Sheynkman
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Abstract

Purpose of review: The underlying molecular mechanisms that direct stem cell differentiation into fully functional, mature cells remain an area of ongoing investigation. Cell state is the product of the combinatorial effect of individual factors operating within a coordinated regulatory network. Here, we discuss the contribution of both gene regulatory and splicing regulatory networks in defining stem cell fate during differentiation and the critical role of protein isoforms in this process.

Recent findings: We review recent experimental and computational approaches that characterize gene regulatory networks, splice regulatory networks, and the resulting transcriptome and proteome they mediate during differentiation. Such approaches include long-read RNA sequencing, which has demonstrated high-resolution profiling of mRNA isoforms, and Cas13-based CRISPR, which could make possible high-throughput isoform screening. Collectively, these developments enable systems-level profiling of factors contributing to cell state.

Summary: Overall, gene and splice regulatory networks are important in defining cell state. The emerging high-throughput systems-level approaches will characterize the gene regulatory network components necessary in driving stem cell differentiation.

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转录因子和剪接因子——干细胞分化的相关调控因子
综述的目的:指导干细胞分化为功能齐全的成熟细胞的基本分子机制仍是一个持续研究的领域。细胞状态是在协调调控网络内运行的各个因子组合效应的产物。在此,我们讨论了基因调控和剪接调控网络在分化过程中对确定干细胞命运的贡献,以及蛋白质同工酶在这一过程中的关键作用:我们回顾了最近的实验和计算方法,这些方法描述了基因调控网络、剪接调控网络以及它们在分化过程中介导的转录组和蛋白质组。这些方法包括长读程 RNA 测序(已证明可对 mRNA 同工酶进行高分辨率剖析)和基于 Cas13 的 CRISPR(可实现高通量同工酶筛选)。总之,基因和剪接调控网络对确定细胞状态非常重要。新出现的高通量系统级方法将表征驱动干细胞分化所必需的基因调控网络成分。
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来源期刊
Current Stem Cell Reports
Current Stem Cell Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
0.00%
发文量
19
期刊介绍: The goal of this journal is to publish cutting-edge reviews on subjects pertinent to all aspects of stem cell research, therapy, ethics, commercialization, and policy. We aim to provide incisive, insightful, and balanced contributions from leading experts in each relevant domain that will be of immediate interest to a wide readership of clinicians, basic scientists, and translational investigators. We accomplish this aim by appointing major authorities to serve as Section Editors in key subject areas across the discipline. Section Editors select topics to be reviewed by leading experts who emphasize recent developments and highlight important papers published over the past year on their topics, in a crisp and readable format. We also provide commentaries from well-known figures in the field, and an Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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