Identifying toggle genes from transcriptome-wide scatter: A new perspective for biological regulation

Giuliani, Alessandro; Bui, Thuy Tien; Helmy, Mohamed; Selvarajoo, Kumar

doi:10.1016/j.ygeno.2021.11.027

Cited by 8 publications

(8 citation statements)

References 49 publications

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“…To reveal the most strongly differentially expressed genes (DEGs), we selected those genes that demonstrated the qualitative difference in expression, i.e., were expressed in the experiment and were not expressed in the control (i.e., switched on in the experiment) or, on the contrary, were expressed in the control and were not expressed in the experiment (i.e., switched off in the experiment). These genes are also termed as toggle genes [ 56 ]. The identification of the switched off and switched on genes enables the identification of NLI-associated qualitative changes in gene regulatory networks and protein interaction networks for proteins encoded by these genes.…”

Section: Resultsmentioning

confidence: 99%

“…The switched on/off (toggle) genes were revealed similarly with the procedure that was used in [ 56 ], but we enhanced it using a two-dimensional histogram instead of a simple scatter plot, not showing gene densities when gene points become too dense and overlapping. Therefore, a two-dimensional histogram allows better discrimination of gaps between peaks, thereby avoiding arbitrary cutoffs.…”

Section: Resultsmentioning

confidence: 99%

“…Such discrete changes may suggest that the genome is undergoing substantial alteration possibly related to chromatin remodeling [ 52 , 53 , 54 ]. The on/off gene switching is more typical for development and cancer cells, which experience profound changes [ 53 , 54 , 55 , 56 ]. The on/off switch in the NLI response suggests that it involves qualitative alteration in gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…Such qualitative differences are a sign that the genome is undergoing substantial changes in expression possibly related to chromatin remodeling [ 52 , 53 , 54 ]. The switched on/off genes were revealed previously both on the transcriptome and proteome levels and are more typical for development and cancer cells, which experience profound changes [ 53 , 54 , 55 , 56 ]. Here we found the on/off gene switching in the NLI response, suggesting that it involves deep, qualitative transcriptomic changes.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Anatskaya

Runov

Ponomartsev

et al. 2023

IJMS

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Many cardiovascular diseases originate from growth retardation, inflammation, and malnutrition during early postnatal development. The nature of this phenomenon is not completely understood. Here we aimed to verify the hypothesis that systemic inflammation triggered by neonatal lactose intolerance (NLI) may exert long-term pathologic effects on cardiac developmental programs and cardiomyocyte transcriptome regulation. Using the rat model of NLI triggered by lactase overloading with lactose and the methods of cytophotometry, image analysis, and mRNA-seq, we evaluated cardiomyocyte ploidy, signs of DNA damage, and NLI-associated long-term transcriptomic changes of genes and gene modules that differed qualitatively (i.e., were switched on or switched off) in the experiment vs. the control. Our data indicated that NLI triggers the long-term animal growth retardation, cardiomyocyte hyperpolyploidy, and extensive transcriptomic rearrangements. Many of these rearrangements are known as manifestations of heart pathologies, including DNA and telomere instability, inflammation, fibrosis, and reactivation of fetal gene program. Moreover, bioinformatic analysis identified possible causes of these pathologic traits, including the impaired signaling via thyroid hormone, calcium, and glutathione. We also found transcriptomic manifestations of increased cardiomyocyte polyploidy, such as the induction of gene modules related to open chromatin, e.g., “negative regulation of chromosome organization”, “transcription” and “ribosome biogenesis”. These findings suggest that ploidy-related epigenetic alterations acquired in the neonatal period permanently rewire gene regulatory networks and alter cardiomyocyte transcriptome. Here we provided first evidence indicating that NLI can be an important trigger of developmental programming of adult cardiovascular disease. The obtained results can help to develop preventive strategies for reducing the NLI-associated adverse effects of inflammation on the developing cardiovascular system.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Anatskaya

Runov

Ponomartsev

et al. 2023

IJMS

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“…These latent attractors display "atavistic" features, being characterized by the increased expression of genes relative to unicellular condition [151,152] and consequently free of the constrains imposed by multi-cellularity to uncontrolled growth (Fig. 2B, right) [153]. The biologic origin of preexisting drug-resistant cells was investigated in recent studies that provided important insights on how cell intrinsic and cell extrinsic factors cooperate to shape this population.…”

Section: Origin and Dynamics Of Drug-resistant Quiescent Cancer Cellsmentioning

confidence: 99%

Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution

Francescangeli

Angelis

Rossi

et al. 2023

Cancer Metastasis Rev

Self Cite

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The biological complexity of cancer represents a tremendous clinical challenge, resulting in the frequent failure of current treatment protocols. In the rapidly evolving scenario of a growing tumor, anticancer treatments impose a drastic perturbation not only to cancer cells but also to the tumor microenvironment, killing a portion of the cells and inducing a massive stress response in the survivors. Consequently, treatments can act as a double-edged sword by inducing a temporary response while laying the ground for therapy resistance and subsequent disease progression. Cancer cell dormancy (or quiescence) is a central theme in tumor evolution, being tightly linked to the tumor’s ability to survive cytotoxic challenges, metastasize, and resist immune-mediated attack. Accordingly, quiescent cancer cells (QCCs) have been detected in virtually all the stages of tumor development. In recent years, an increasing number of studies have focused on the characterization of quiescent/therapy resistant cancer cells, unveiling QCCs core transcriptional programs, metabolic plasticity, and mechanisms of immune escape. At the same time, our partial understanding of tumor quiescence reflects the difficulty to identify stable QCCs biomarkers/therapeutic targets and to control cancer dormancy in clinical settings. This review focuses on recent discoveries in the interrelated fields of dormancy, stemness, and therapy resistance, discussing experimental evidences in the frame of a nonlinear dynamics approach, and exploring the possibility that tumor quiescence may represent not only a peril but also a potential therapeutic resource.

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Harnessing the power of proteomics in precision diabetes medicine

Kurgan,

Kjærgaard Larsen,

Deshmukh

2024

Diabetologia

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Identifying toggle genes from transcriptome-wide scatter: A new perspective for biological regulation

Cited by 8 publications

References 49 publications

Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution

Harnessing the power of proteomics in precision diabetes medicine

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