Transcription factors and splice factors - interconnected regulators of stem cell differentiation - PubMed
Transcription factors and splice factors - interconnected regulators of stem cell differentiation
Madison M Mehlferber et al. Curr Stem Cell Rep. 2023 Jun.
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.
Keywords: Alternative Splicing; Development; Regulatory Networks; Splice Factors; Stem cells; Transcription Factors.
Conflict of interest statement
Conflict of interest: Madison M. Mehlferber, Muge Kuyumcu, Gloria M. Sheynkman declare they have no conflict of interest. Clint L. Miller has received funding support from AstraZeneca for work unrelated to the current study.
Figures
Demonstration of gene regulatory networks and splice regulatory networks
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