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1. Impact of histone post-translational modification inhibitors on lifespan, reproduction, and stress response in the rotifer Brachionus manjavacas

   https://doi.org/10.1371/journal.pone.0324769  

   Luviano_Aparicio, Nelia; Dryburgh, Meghan; McMaken, Colleen M; Liguori, Alyssa; Gribble, Kristin E (October 2025, PLOS One)

   Sirigiri, Divijendra_Natha Reddy (Ed.)

   Epigenetic modifications, including histone post-translational modifications, are central drivers of age-associated structural and functional changes in the genome, influencing gene expression and leading to changes in cellular resilience. Epigenetic modifications are thus a target for therapies to prevent or treat age-related decline in health and lifespan. In this study, we measured the effects of inhibiting histone deacetylases (HDACs) and the histone methyltransferase, SETDB1, on lifespan, reproduction, and stress response in the rotiferBrachionus manjavacas, a model organism for aging studies. Rotifers were exposed to three pharmaceutical compounds, the HDAC inhibitors β-hydroxybutyrate and sodium butyrate and the SETDB1 inhibitor mithramycin A. Changes in global histone modification levels, lifespan, reproduction, and heat stress resistance were quantified. Global histone acetylation levels increased with β-hydroxybutyrate and sodium butyrate treatments. Histone 3 lysine 9 trimethylation (H3K9me3) levels were reduced by treatment with mithramycin A. β-hydroxybutyrate significantly extended lifespan without modifying heat stress resistance. In contrast, mithramycin A increased both lifespan and heat stress tolerance. Sodium butyrate specifically improved heat stress resistance without affecting lifespan. Importantly, none of the three treatments had a significant impact on lifetime reproduction. These findings provide insights into the role of histone modifications in aging and suggest potential interventions targeting epigenetic marks to promote longevity and resilience. 

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2. Pre-Clinical Cell Therapeutic Approaches for Repair of Volumetric Muscle Loss

   https://doi.org/10.3390/bioengineering7030097  

   Shayan, Mahdis; Huang, Ngan F. (September 2020, Bioengineering)

   Extensive damage to skeletal muscle tissue due to volumetric muscle loss (VML) is beyond the inherent regenerative capacity of the body, and results in permanent functional debilitation. Current clinical treatments fail to fully restore native muscle function. Recently, cell-based therapies have emerged as a promising approach to promote skeletal muscle regeneration following injury and/or disease. Stem cell populations, such as muscle stem cells, mesenchymal stem cells and induced pluripotent stem cells (iPSCs), have shown a promising capacity for muscle differentiation. Support cells, such as endothelial cells, nerve cells or immune cells, play a pivotal role in providing paracrine signaling cues for myogenesis, along with modulating the processes of inflammation, angiogenesis and innervation. The efficacy of cell therapies relies on the provision of instructive microenvironmental cues and appropriate intercellular interactions. This review describes the recent developments of cell-based therapies for the treatment of VML, with a focus on preclinical testing and future trends in the field. 

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3. Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity

   https://doi.org/10.1038/s41467-025-59190-7  

   Wu, Yifan; Song, Yang; Soto, Jennifer; Hoffman, Tyler; Lin, Xiao; Zhang, Aaron; Chen, Siyu; Massad, Ramzi N; Han, Xiao; Qi, Dongping; et al (December 2025, Nature Communications)

   Abstract Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function, compared to those on elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility atcis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering. 

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4. Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine

   https://doi.org/10.3389/fbioe.2025.1581292  

   Cruz-Gonzalez, Brenda; Johandes, Ellie; Gramm, Dominique; Hanjaya-Putra, Donny (May 2025, Frontiers in Bioengineering and Biotechnology)

   Biomaterial-assisted stem cell therapies hold immense promise for regenerative medicine, yet clinical translation remains challenging. This review focuses on recent advances and persistent limitations in applying induced pluripotent stem cells (iPSCs), endothelial colony-forming cells (ECFCs), multipotent mesenchymal stromal cells (MSCs), and embryonic stem cells (ESCs) within engineered microenvironments. We introduce a novel “bottom-up” approach to biomaterial design. This approach focuses first on understanding the fundamental biological properties and microenvironmental needs of stem cells, then engineering cell-instructive biomaterials to support them. Unlike conventional methods that adapt cells to pre-existing materials, this strategy prioritizes designing biomaterials from the molecular level upward to address key challenges, including differentiation variability, incomplete matching of iPSCs to somatic counterparts, functional maturity of derived cells, and survival of ECFCs/MSCs in therapeutic niches. By replicating lineage-specific mechanical, chemical, and spatial cues, these tailored biomaterials enhance differentiation fidelity, reprogramming efficiency, and functional integration. This paradigm shift from passive scaffolds to dynamic, cell-instructive platforms bridges critical gaps between laboratory success and clinical translation, offering a transformative roadmap for regenerative medicine and tissue engineering. 

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5. Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts

   https://doi.org/10.3390/biom12010029  

   Mandal, Susmita; Tejaswi, Tanishq; Janivara, Rohini; Srikrishnan, Syamanthak; Thakur, Pradipti; Sahoo, Sarthak; Chakraborty, Priyanka; Sohal, Sukhwinder Singh; Levine, Herbert; George, Jason T.; et al (January 2022, Biomolecules)

   Epithelial-mesenchymal plasticity (EMP) underlies embryonic development, wound healing, and cancer metastasis and fibrosis. Cancer cells exhibiting EMP often have more aggressive behavior, characterized by drug resistance, and tumor-initiating and immuno-evasive traits. Thus, the EMP status of cancer cells can be a critical indicator of patient prognosis. Here, we compare three distinct transcriptomic-based metrics—each derived using a different gene list and algorithm—that quantify the EMP spectrum. Our results for over 80 cancer-related RNA-seq datasets reveal a high degree of concordance among these metrics in quantifying the extent of EMP. Moreover, each metric, despite being trained on cancer expression profiles, recapitulates the expected changes in EMP scores for non-cancer contexts such as lung fibrosis and cellular reprogramming into induced pluripotent stem cells. Thus, we offer a scoring platform to quantify the extent of EMP in vitro and in vivo for diverse biological applications including cancer. 

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