Author response: Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells

Kafri, Pinhas; Hasenson, Sarah E; Kanter, Itamar; Sheinberger, Jonathan; Kinor, Noa; Yunger, Sharon; Shav‐Tal, Yaron

doi:10.7554/elife.16748.036

Cited by 2 publications

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WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

Ross,

Azami,

Salonna

et al. 2024

Preprint

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Embryonic stem cell research has uncovered different requirements for WNT/beta-catenin signalling in human naive pluripotent cells compared to the mouse paradigm. It is therefore important to study WNT/beta-catenin signalling directly in models of early human development. Since TCF/LEF factors mediate the regulation of target genes downstream of WNT/beta-catenin signalling, we studied the expression and protein localisation of the four TCF/LEF genes by analysing in vitro snapshots of human development, leveraging naive and primed pluripotent cells as well as extraembryonic and early embryonic cell lineages. Strikingly, we comprehensively confirm clear differences between mouse and human pluripotent stem cells, suggesting species-specific requirements for WNT signalling that may reflect differences in states of pluripotency. Human naive ES cells express very low TCF7L1, unlike their mouse counterparts. TCF7L2 is robustly expressed in human naive ES-derived trophectoderm cells. In human primed pluripotent stem cells, activation of WNT/beta-Catenin signalling is required to induce expression of both TCF7 and LEF1, concomitant with hallmark gastrulation markers. This expression of human TCF/LEF genes benchmarks differential requirements for WNT/beta-catenin signalling throughout early human embryo development that requires further investigation.

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WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

Ross,

Azami,

Salonna

et al. 2024

Preprint

View full text Add to dashboard Cite

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Transcriptional bursting dynamics in gene expression

Zhang,

Cao,

Wang

et al. 2024

Front. Genet.

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Gene transcription is a stochastic process that occurs in all organisms. Transcriptional bursting, a critical molecular dynamics mechanism, creates significant heterogeneity in mRNA and protein levels. This heterogeneity drives cellular phenotypic diversity. Currently, the lack of a comprehensive quantitative model limits the research on transcriptional bursting. This review examines various gene expression models and compares their strengths and weaknesses to guide researchers in selecting the most suitable model for their research context. We also provide a detailed summary of the key metrics related to transcriptional bursting. We compared the temporal dynamics of transcriptional bursting across species and the molecular mechanisms influencing these bursts, and highlighted the spatiotemporal patterns of gene expression differences by utilizing metrics such as burst size and burst frequency. We summarized the strategies for modeling gene expression from both biostatistical and biochemical reaction network perspectives. Single-cell sequencing data and integrated multiomics approaches drive our exploration of cutting-edge trends in transcriptional bursting mechanisms. Moreover, we examined classical methods for parameter estimation that help capture dynamic parameters in gene expression data, assessing their merits and limitations to facilitate optimal parameter estimation. Our comprehensive summary and review of the current transcriptional burst dynamics theories provide deeper insights for promoting research on the nature of cell processes, cell fate determination, and cancer diagnosis.

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Author response: Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells

Cited by 2 publications

References 0 publications

WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

Transcriptional bursting dynamics in gene expression

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