scholarly journals m6A-mediated Cell-cell Communication Controls Planarian Regeneration

2021 ◽  
Author(s):  
Guanshen Cui ◽  
Jia-Yi Zhou ◽  
Xin-Yang Ge ◽  
Bao-Fa Sun ◽  
Ge-Ge Song ◽  
...  
Keyword(s):  
Adult Stem Cells ◽  
Cell Communication ◽  
Whole Body ◽  
Regulatory Subunit ◽  
Cell Renewal ◽  
Specific Expression ◽  
Unique Type ◽  
Planarian Regeneration ◽  
Underlying Mechanisms ◽  
Cell Cell

Regeneration is the regrowth of damaged tissues or organs, a vital mechanism responding to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owning to its vast reservoir of adult stem cells, neoblasts, thus provides an ideal model to delineate the underlying mechanisms for regeneration. N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. However, how m6A controls regeneration at whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6A methyltransferase regulatory subunit wtap abolishes planarian regeneration, through regulating cell-cell communication and cell cycle. scRNA-Seq analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6A-modified transcripts grn/cdk9 (or cdk7) axis rescues the defective regeneration of planarian without wtap. Overall, our study reveals an indispensable role of m6A-dependent cell-cell communication essential for whole-organism regeneration.

scholarly journals Cooperation between oncogenic Ras and p53 stimulates JAK/STAT non-cell autonomously to promote Ras tumor radioresistance

2020 ◽  
Author(s):  
Yong-Li Dong ◽  
Ganghadara P Valdka ◽  
Jin-Yu (Jim) Lu ◽  
Vakil Ahmad ◽  
Thomas J. Klein ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cellular Response ◽  
Cell Communication ◽  
Genotoxic Stress ◽  
Tumor Resistance ◽  
Therapy Outcomes ◽  
Oncogenic Ras ◽  
Tumor Tissues ◽  
Underlying Mechanisms ◽  
Cell Cell

AbstractOncogenic RAS mutations are associated with tumor resistance to radiation therapy. The underlying mechanisms remain unclear. Emergent cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. The nature of these interactions and their role in Ras tumor radioresistance remain unclear. We used Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discovered that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. JAK/STAT accelerates the growth of the less-damaged Ras tumor cells, leading to rapid tumor recurrence. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. This finding suggests that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients.

Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’: Stem Cells and Cell-Cell Communication as Fundamental Targets in Assessing the Potential Toxicity of Chemicals

2010 ◽  
Vol 29 (1) ◽  
pp. 21-29 ◽  
Author(s):  
James E Trosko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Health Effects ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Cell Communication ◽  
Toxicity Testing ◽  
Scientific Understanding ◽  
Cell Cell

Faced with the reality of our current methods of drug discovery and toxicity assessment of all chemicals is less than perfect, the Report, ‘‘Toxicity Testing in the 21 st Century: A Vision and a Strategy’’, posed a reality check on all scientific efforts to find new conceptual and technical approaches for being better predictors of potential human health effects. This Commentary is a challenge to both the current paradigms and techniques to test chemicals for their potential toxicities. While, clearly, our scientific understanding of the mechanisms of chemical-induced toxicity and of the pathogeneses of all human diseases are not complete, the state of scientific understanding seems not only sufficient to know what we are now doing is not sufficient, but that it is adequate enough to make a new paradigm and technological change. Basically, the challenge includes the opinion that human exposure to chemicals, that are associated with one or more health endpoints (birth defects, cardiovascular diseases, cancer, reproductive and neurological dysfunctions), is the result of epigenetic , not mutagenic or genotoxic, mechanisms. In addition, it is postulated that the adult human stem cell should be considered the ‘‘target’’ cell for the important chemical-induced health effects. To test this hypothesis that altering the quantity and quality of adult stem cells by chemical exposures during in utero, neonatal, adolescent, adult and geriatric phases of life can lead to health consequences, it is recommended that 3-D in vitro cultures be used on male and female human adult stem cells from a few major organs (e.g., heart, brain, liver, lung, kidney, breast, prostate ). Altered stem cell biology (e.g., increase or decrease in the stem cell numbers in specific organs; altered apoptotic and differentiation frequencies), as well as measured cell-cell communication, should be seriously considered as toxicity endpoints.

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