Developmental epigenomic fidelity in stem cell and organoid models

Animal development is accompanied by extensive and highly coordinated epigenomic reprogramming. During germline development, fertilization, preimplantation development, early lineage specification, and embryo development, DNA methylation, genomic imprinting, chromatin accessibility, histone modifications, and three-dimensional genome organization are remodeled. These processes are essential for resetting developmental potential and establishing cell identities. Advances in stem cell biology, cellular reprogramming, organoid technology, embryo-like models, and single-cell multi-omics have created unprecedented opportunities to investigate these events in vitro. Such systems are increasingly used to model early development, study infertility and congenital disease, and support applications in regenerative medicine and biotechnology. However, the extent to which they reproduce the epigenomic states and trajectories observed in vivo remains incompletely understood.Recent studies have revealed both the strengths and limitations of current in vitro models. ESC and iPSC systems can reproduce aspects of pluripotency and lineage specification, while organoids, gastruloids, and embryo-like models can capture selected features of tissue organization and developmental progression. Nevertheless, these systems may display incomplete epigenomic resetting, persistent somatic memory, aberrant DNA methylation, imprint instability, and culture-induced transcriptional and epigenomic abnormalities. Differences in species, genetic background, reprogramming strategy, culture conditions, and developmental timing further complicate comparisons between models. Although single-cell and multi-omic approaches are beginning to define developmental reference maps, the field still lacks widely accepted criteria and quantitative benchmarks for determining whether an in vitro system faithfully recapitulates an in vivo developmental state. Systematic comparisons, functional validation, and improved standards are therefore needed to establish the biological relevance, reproducibility, and limitations of these models.This Research Topic aims to advance the assessment and improvement of developmental epigenomic fidelity in vitro. We particularly welcome studies that compare in vivo and in vitro developmental trajectories, identify the molecular basis and functional consequences of model-specific deviations, and develop experimental or computational strategies to improve model fidelity. Contributions that establish reference epigenomic maps, define quantitative benchmarks, evaluate the effects of culture or reprogramming conditions, or link epigenomic states to lineage potential and developmental competence are especially encouraged. The Research Topic focuses on developmental epigenomic reprogramming and its faithful representation in vitro, rather than on epigenomic changes across aging, disease progression, or the entire developmental lifespan.To gather further insights into the mechanisms, assessment, and improvement of developmental epigenomic fidelity in vitro, we welcome articles addressing the following themes:Mechanisms of developmental epigenomic reprogramming• Epigenomic reprogramming during germline specification, gametogenesis, fertilization, preimplantation development, and early lineage commitment• DNA methylation erasure, resetting, and remethylation, and the establishment and maintenance of genomic imprinting• Chromatin accessibility, histone modifications, histone variants, and three-dimensional genome organization during developmental transitions• Comparative analyses of in vivo and in vitro developmental epigenomic trajectoriesModel systems and fidelity assessment• ESC and iPSC differentiation models of early developmental processes• Somatic cell reprogramming and the acquisition of pluripotent or developmental states• Organoids, gastruloids, blastoids, and other three-dimensional embryo-like systems• Single-cell, spatial, and multi-omic profiling of developmental model systems• Computational reconstruction and comparison of developmental trajectories• Quantitative benchmarks, reference maps, and standards for assessing model fidelitySources of deviation and strategies for improvement• Culture-induced epigenomic alterations, incomplete reprogramming, and imprint instability in stem cell and embryo-like models• Effects of species, genetic background, culture conditions, and reprogramming protocols• Functional validation of epigenomic states through lineage potential and developmental competence• Strategies to improve the fidelity and reproducibility of stem cell, organoid, and embryo-like modelsWe welcome Original Research, Reviews, Mini Reviews, Methods, and Perspectives. Topic editors: Tristan Bouschet, Linkai Zhu Source: https://www.frontiersin.org/research-topics/85448/developmental-epigenomic-fidelity-in-stem-cell-and-organoid-models