Long-term video-based tracking of single A549 lung cancer cells exposed to three different concentrations of the marine toxin yessotoxin (YTX) reveals significant variation in cytotoxicity, and it confirms the potential genotoxic effects of this toxin. Tracking of single cells subject to various toxic exposure, constitutes a conceptually simple approach to elucidate lineage correlations and sub-populations which are masked in cell bulk analyses. The toxic exposure can here be considered as probing a cell population for properties and change which may include long-term adaptation to treatments. Ranking of pedigree trees according to a measure of "size," provides definition of sub-populations. Following single cells through generations indicates that signaling cascades and experience of mother cells can pass to their descendants. Epigenetic factors and signaling downstream lineages may enhance differences between cells and partly explain observed heterogeneity in a population. Signaling downstream lineages can potentially link a variety of observations of cells making resulting data more suitable for computerized treatment. YTX exposure of A549 cells tends to cause two main visually distinguishable classes of cell death modalities ("apoptotic-like" and "necrotic-like") with approximately equal frequency. This special property of YTX enables estimation of correlation between cell death modalities for sister cells indicating impact downstream lineages. Hence, cellular responses and adaptation to treatments might be better described in terms of effects on pedigree trees rather than considering cells as independent entities.
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http://dx.doi.org/10.3389/fonc.2018.00260 | DOI Listing |
Cancer Sci
December 2024
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan.
KRAS was long deemed undruggable until the discovery of the switch-II pocket facilitated the development of specific KRAS inhibitors. Despite their introduction into clinical practice, resistance mechanisms can limit their effectiveness. Initially, tumors rely on mutant KRAS, but as they progress, they may shift to alternative pathways, resulting in intrinsic resistance.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
Understanding how embryonic progenitors decode extrinsic signals and transform into lineage-specific regulatory networks to drive cell fate specification is a fundamental, yet challenging question. Here, we develop a new model of surface epithelium (SE) differentiation induced by human embryonic stem cells (hESCs) using retinoic acid (RA), and identify BMP4 as an essential downstream signal in this process. We show that the retinoid X receptors, RXRA and RXRB, orchestrate SE commitment by shaping lineage-specific epigenetic and transcriptomic landscapes.
View Article and Find Full Text PDFUnlabelled: Megakaryocytes (MKs) are large, polyploid cells that contribute to bone marrow homeostasis through the secretion of cytokines such as transforming growth factor β1 (TGFβ1). During neoplastic transformation, immature MKs accumulate in the bone marrow where they induce fibrotic remodeling ultimately resulting in myelofibrosis. Current treatment strategies aim to prevent MK hyperproliferation, however, little is understood about the potential of targeting dysregulated cytokine secretion from neoplastic MKs as a novel therapeutic avenue.
View Article and Find Full Text PDFZootaxa
August 2024
Section of Research & Collections; North Carolina Museum of Natural Sciences; North Carolina; 27601; USA.
Elife
December 2024
Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States.
Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) plays a critical role in craniofacial development. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during mouse skeletal development. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRα signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation.
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