Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

Mammalian fertilization initiates the reprogramming of oocytes and sperm, leading to the formation of a totipotent zygote. The zygotic genome remains transcriptionally silent throughout this intricate process, undergoing the maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA). Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis enable a detailed exploration of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts, ranging from regenerative medicine to cancer research. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells and the subsequent loss of insulin production. The regeneration of pancreatic β-cells from induced pluripotent stem cells (iPSCs) represents a promising therapeutic approach for restoring β-cell function in T1DM patients. However, ensuring the safety, functionality, and genetic stability of iPSC-derived β-cells is crucial for their clinical application. To address this challenge, a comprehensive literature review was conducted using PubMed/MEDLINE, Web of Science, and Scopus databases to identify relevant studies published up to October 2025. It included an analysis of key regulatory documents from the U.S. Food and Drug Administration (FDA), the European Medicines Agency on Advanced Therapy Medicinal Products (EMA ATMP), and the International Organization for Standardization (ISO). This article proposes a comprehensive quality control (QC) strategy for differentiating iPSCs into pancreatic β-cells, emphasizing a tiered approach with multiple checkpoints throughout the process. The strategy integrates advanced molecular and functional assays to evaluate cell identity, viability, stability, and microbiological safety. The proposed QC framework allows for continuous monitoring, early detection of potential issues, and real-time adjustments to optimize the differentiation process. The flexibility of this approach ensures its adaptation to emerging scientific advancements and regulatory requirements. This integrated and adaptable QC strategy enhances the likelihood of success in generating functional β-cells, laying a solid foundation for the clinical application of iPSC-derived β-cell therapies and offering hope for effective, long-term treatments for T1DM.