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Stem cell-based embryo models provide an alternative system to study an elusive period of development. Programmed mouse embryo models have recently been generated by activating two endogenous regulatory elements via epigenome editing. In this forum article, we discuss this achievement along with the potential of translating it to engineering models of human embryogenesis.
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http://dx.doi.org/10.1016/j.tcb.2025.08.003 | DOI Listing |
Nat Cell Biol
September 2025
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Durotaxis, cell migration along stiffness gradients, is linked to embryonic development, tissue repair and disease. Despite solid in vitro evidence, its role in vivo remains largely speculative. Here we demonstrate that durotaxis actively drives disease progression in vivo in mouse models of lung fibrosis and metastatic pancreatic cancer.
View Article and Find Full Text PDFJCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China.
EZH2 catalyzes H3K27me3 and is essential for embryonic development. Although multiple EZH2 variants have been identified, the functional implications and physiological significance of its heterogeneity remain unclear. Here, we revealed that conserved cryptic splice sites generated two EZH2 variants with (EZH2A) or without (EZH2B) a 27-nt region, coding for a 9-aa segment.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
September 2025
Department of Biological Sciences, Clemson University, Clemson, SC, USA; Clemson University Center for Human Genetics, Greenwood, SC, USA. Electronic address:
Tetrabromobisphenol A (TBBPA), a widely used flame retardant in textiles and electronics, poses toxicological risks through both environmental and indoor exposures. Biomonitoring studies have detected significant TBBPA levels in prenatal environments, including cord blood, raising concerns about developmental impacts. Using zebrafish as a model, this study addresses critical gaps in understanding how developmental TBBPA exposures perturb regulatory pathways that govern dorsoventral patterning.
View Article and Find Full Text PDFExp Hematol
September 2025
Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan. Electronic address:
Gene rearrangements of the human MLL gene (also known as KMT2A) generate multiple fusion oncoproteins which cause leukemia with poor prognosis. MLL is an epigenetic regulator that reads and writes epigenetic information and has an evolutionarily conserved role maintaining expression of Homeotic (HOX) genes during embryonic development. Most MLL gene rearrangements found in leukemia generate a constitutively active version of the wild-type protein, which causes overexpression of HOX and other genes and leukemic transformation of normal hematopoietic progenitors.
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