Dataset Information

Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

ABSTRACT: The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, and receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing EMT by TGF-β1 stimulation. Our comprehensive analysis revealed that cells progress through EMT at different paces. Using pseudotime clustering reconstruction of gene-expression profiles during EMT, we found sequential and parallel activation of EMT signaling pathways. We also observed various transitional cellular states during EMT. We identified regulatory signaling nodes that drive EMT with the expression of important microRNAs and transcription factors. Using a random circuit perturbation methodology, we demonstrate that the NOTCH signaling pathway acts as a key driver of TGF-β-induced EMT. Furthermore, we demonstrate that the gene signatures of pseudotime clusters corresponding to the intermediate hybrid EMT state are associated with poor patient outcome. Overall, this study provides insight into context-specific drivers of cancer progression and highlights the complexities of the EMT process.

SUBMITTER: Deshmukh AP

PROVIDER: S-EPMC8126782 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

Deshmukh Abhijeet P AP Vasaikar Suhas V SV Tomczak Katarzyna K Tripathi Shubham S den Hollander Petra P Arslan Emre E Chakraborty Priyanka P Soundararajan Rama R Jolly Mohit Kumar MK Rai Kunal K Levine Herbert H Mani Sendurai A SA

Proceedings of the National Academy of Sciences of the United States of America 20210501 19

The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, and receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing EMT by TGF-β1 stimulation. Our comprehensive analysis revealed that cells progress through EMT at different paces. Using pseudotime clustering reconstruction of gene-expr ...[more]

PMID: 33941680

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Project description:Cucumber is a model plant for studying parthenocarpy with abundant slicing- and pickling-type germplasm. This study was undertaken to understand the role of the important cytokines (CKs), auxin (AUX) and gibberellin (GA) biosynthesis and degradation genes for the induction of parthenocarpy in slicing and pickling germplasm. Two genotypes of gynoecious parthenocarpic cucumber, PPC-6 and DG-8, along with an MABC-derived gynoecious non-parthenocarpic line, IMPU-1, were evaluated in this study. The slicing and pickling cucumber genotypes PPC-6 and DG-8 were strongly parthenocarpic in nature and set fruit normally without pollination. Endogenous auxin and gibberellin were significantly higher in parthenocarpic than non-parthenocarpic genotypes, whereas the concentration of cytokinins varied among the genotypes at different developmental stages. However, the exogenous application of Zeatin and IAA + Zeatin was effective in inducing parthenocarpic fruit in IMPU-1. Expression analysis with important CK, AUX, and GA biosynthesis-related genes was conducted in IMPU-1, PPC-6, and DG-8. The expression of the CK synthase, IPT, IPT3, PaO, LOG1, LOG2, CYP735A1, and CYP735A2 was up-regulated in the parthenocarpic genotypes. Among the transcription factor response regulators (RRs), positive regulation of CSRR8/9b, CSRR8/9d, CSRR8/9e, and CSRR16/17 and negative feedback of the CK signalling genes, such as CsRR3/4a, CsRR3/4b, CsRR8/9a, and CsRR8/9c, were recorded in the parthenocarpic lines. Homeostasis between cytokinin biosynthesis and degradation genes such as CK oxidases (CKXs) and CK dehydrogenase resulted in a non-significant difference in the endogenous CK concentration in the parthenocarpic and non-parthenocarpic genotypes. In addition, up-regulation of the key auxin-inducing proteins and GA biosynthesis genes indicated their crucial role in the parthenocarpic fruit set of cucumber. This study establishes the critical role of the CKs, AUX, and GA regulatory networks and their cross-talk in determining parthenocarpy in slicing and pickling cucumber genotypes.

Dataset Information

Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

Publications

Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

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