achieving-high-quality-tomographic-data-collection-using-200-kv

Achieving High-Quality Tomographic Data Collection Using the 200 kV Transmission Electron Microscope with Dual Condenser Lens System

Cryo-electron tomography (cryo-ET) has emerged as a powerful technique for elucidating the structures of cellular organelles and large protein complexes ...

Peking University Third Hospital

Beijing Key Laboratory of Collaborative Innovation in Frontier Technologies for Population Quality

 Melanoma, the deadliest form of skin cancer characterized by high therapy resistance, has undergone extensive investigation through the utilization of BRAF-driven melanoma animal models. However, there exists a paucity of animal models for the rare hereditary melanoma resulting from germline  mutations.  Here, employing CRISPR/Cas9 technology, we generated  on a  knockout background to model human  germline mutation-induced hereditary melanoma.  The findings unveiled that  frogs spontaneously developed melanoma, pancreatic cancer, and other tumors. Specifically, these frogs exhibited a high penetrance of spontaneous melanoma, sharing characteristics with melanomas in human hereditary melanoma caused by germline  mutations. During melanoma development in  frogs, the occurrences of epithelial-to-mesenchymal transition, the reactivation of pigment cell progenitor cell transcriptional states, and the activation in the MAPK, NF-kB, PI3K-Akt, and TGF-β signaling pathways were noted.  Overall,  provides a vertebrate model for investigating the development of  germline mutation-induced hereditary melanoma, contributing to the exploration of the pathogenesis of hereditary melanoma in humans.

High frequency of melanoma in  /.

Melanin pigmentation in oocytes is a critical feature for both the esthetic and developmental aspects of oocytes, influencing their polarity and overall development. Despite substantial knowledge of melanogenesis in melanocytes and retinal pigment epithelium cells, the molecular mechanisms underlying oocyte melanogenesis remain largely unknown.

Melanin deposition and key molecular features in Xenopus tropicalis oocytes.

Pigment cells not only are intrinsic factors to determine animal patterns, but also play vital roles in numerous behavioral and physiological processes as well as health, such as melanomas originating from melanocytes. Model organisms are commonly used to study pigment cell development and the mechanisms underlying related diseases, with zebrafish and mice, and Xenopus being well-established examples. Xenopus tropicalis, a diploid amphibian model, offers advantages such as high fecundity and easily observable pigment cell development. Recent advancements in gene-editing techniques have increased its prominence in research on pigment cell biology and melanoma pathogenesis. Here, we compare the skin pigment cell distribution as well as the skin structure in X. tropicalis, zebrafish, mice, and humans and point out the potential value of using X. tropicalis to model human skin diseases, such as melanoma.

Cutaneous Pigment Cell Distributions and Skin Structure of Xenopus.

The melanocortin 1 receptor (MC1R) is well-established as a pivotal regulator of pigmentation in various species. Despite a wealth of research focused on mammals and fish, the role of Mc1r in amphibians has remained largely unexplored. This study was designed to elucidate the contribution of Mc1r in Xenopus tropicalis. Our results reveal that targeted ablation of mc1r in Xenopus tropicalis led to a significant reduction in dorsal skin pigmentation, while simultaneously accelerating the onset of melanophore pigmentation in the ventral region. This dual effect resulted in a perturbation of the canonical countershading pattern. Additionally, knockout of mc1r disrupted the expression of multiple genes primarily associated with pigmentation. Collectively, these findings underscore the critical role of MC1R in the regulation of pigmentation and the development of countershading in amphibians, contributing to the growing body of literature on the evolution and function of MC1R across vertebrate species.

Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis.

Targeting exogenous gene integrations in animals often exhibits low efficiency, limiting the development of gene knock-in models. Theoretically, by screening founder generation individuals based on the cell phenotypes resulting from gene knock-ins and leveraging the high fecundity of animals, heritable descendants with targeted knock-ins can be efficiently generated. Therefore, we utilized the high fecundity of  and easily observable pigment phenotypes to construct a -targeted  locus knock-in model. Results indicated that this approach enabled efficient generation of  knock-in  and produced a versatile frog model. The  knock-in induced the transdifferentiation of RPE cells into retinal cells, resulting in a symmetric retinal structure in the eyes of these frogs. The transformation of RPE cells ultimately leads to these frogs becoming eyeless frogs, which serve as a tool for retinal regeneration research. Additionally, in eyeless frogs the  knock-in led to the abnormal proliferation of both melanocytes and xanthophores into melanocytic and xanthocytic nevi respectively. Consequently, eyeless frogs provide a model for studying abnormal pigment cell proliferation, offering a platform for investigating pigment cell nevus formation. Furthermore, the -knockout eyeless frogs serve as a valuable xanthophoroma model for tumor biology research. Overall, the -targeted knock-in  not only represents a strategy for constructing gene knock-in animal models but also serves as a versatile tool for research in retinal regeneration and tumor biology.

Versatile  model with targeted integration of human .

Skin cutaneous melanoma (SKCM) is a highly invasive malignant tumor with poor prognosis in the advanced stage and prominent problems of immunotherapy resistance. Heat shock protein A8 (HSPA8) is involved in tumor progression and immune escape in various cancers, but its role in SKCM remains unclear. This study aimed to explore the role of HSPA8 in SKCM.

HSPA8 is a biomarker associated with prognosis and immunity in skin cutaneous melanoma.

B‑lymphocytes (B‑cells) develop from hematopoietic stem cells in the bone marrow or fetal liver and differentiate into antibody‑secreting cells and memory B‑cells upon encountering antigens in peripheral lymphoid organs. Throughout this process, the expression of lineage‑associated genes is upregulated, whereas that of lineage‑inappropriate genes is repressed, thereby directing commitment to a specific B‑cell fate. Epigenetic regulatory mechanisms, including DNA methylation, post‑translational histone modifications and non‑coding RNAs, regulate gene transcription and play crucial roles in B‑cell development and differentiation. The dysregulation of these epigenetic processes may contribute to the pathogenesis of autoimmune diseases and B‑cell malignancies. Recent advances in high‑throughput techniques, including single‑cell RNA sequencing, chromatin immunoprecipitation‑sequencing and whole‑genome bisulfite sequencing, have significantly enhanced the understanding of epigenetic dysregulation in these disorders. The present review summarizes recent advances in the understanding of dysregulated epigenetic mechanisms underlying B‑cell‑mediated autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis and type 1 diabetes mellitus) and lymphomas (such as diffuse large B‑cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma and marginal zone lymphoma), and highlights emerging diagnostic biomarkers and therapeutic strategies.

Article	Year
High frequency of melanoma in /. Theranostics\| PubMed ID: 39659584	2024
Melanin deposition and key molecular features in Xenopus tropicalis oocytes. BMC biology\| PubMed ID: 40016733	2025
Cutaneous Pigment Cell Distributions and Skin Structure of Xenopus. Pigment cell & melanoma research\| PubMed ID: 40329555	2025
Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis. Pigment cell & melanoma research\| PubMed ID: 40524449	2025
Versatile model with targeted integration of human . Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 41004227	2025
HSPA8 is a biomarker associated with prognosis and immunity in skin cutaneous melanoma. Discover oncology\| PubMed ID: 41486312	2026
Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review). International journal of molecular medicine\| PubMed ID: 41574706	2026

Rensen Ran

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