摘要: The black rockfish (Sebastes schlegelii) is a marine species that is economically important in aquaculture, and the efficiency of its spermatogenesis is vital for its success in the aquaculture industry. Spermatogonia serve as the foundation of spermatogenesis in fish, possessing the ability for continuous self-renewal and progressive differentiation into mature spermatozoa. Moreover, Sertoli cells are crucial in modulating the proliferation and differentiation of spermatogonia. This study focused on the regulation of glycolysis by PLIN2a in Sertoli cells of the black rockfish and examined how the inhibition of glycolysis in these cells impacted the proliferation and differentiation processes of spermatogonia. We found that effective regulation of glycolysis was crucial for the metabolic activity and functional maintenance of Sertoli cells in black rockfish. Overexpression of plin2a in vitro enhanced glycolysis in Sertoli cells, whereas inhibition of glycolysis impaired their normal metabolic activity. In vivo inhibition of glycolysis in black rockfish testes lead to apoptosis of Sertoli cells and significantly suppressed the proliferation and differentiation of spermatogonia. These results underscore the essential role of glycolysis in the development and metabolic activity of Sertoli cells and highlight the critical regulatory role of glycolysis in determining the fate of spermatogonia. This study emphasizes the importance of regulating energy metabolism pathways, particularly glycolysis, in Sertoli cells to indirectly influence the development of spermatogonia, offering significant insights into the reproductive mechanisms of black rockfish and other teleost species.

摘要: Astrocytes are crucial for central nervous system (CNS) development and function, with their differentiation being stringently controlled by epigenetic mechanisms, such as histone modifications. Enhancer of Zeste Homologue 2 (EZH2), a histone methyltransferase, is essential for the suppression of gene expression. However, the role of EZH2 in astrocyte early morphogenesis has remained unclear. Using an astrocyte-specific Ezh2 knockout (cKO) mouse model, we examined the effects of EZH2 deletion on astrocyte morphogenesis, blood-brain barrier (BBB) integrity and neurodevelopment. Loss of EZH2 led to increased glial fibrillary acidic protein (GFAP) expression, altered astrocyte morphology and reduced coverage of astrocytic endfeet on blood vessels, compromising BBB integrity. Vascular abnormalities, characterised by increased vascular density and smaller vessel diameter, mirrored compensatory changes seen in moyamoya disease. RNA-sequencing and ChIP-seq identified Ddn as a key upregulated gene in Ezh2cKO astrocytes, influencing cytoskeletal changes via the MAPK/ERK pathway. Behavioural analysis revealed autism-like traits, such as reduced vocalisations, without significant anxiety-like behaviour. These findings highlight EZH2 as a critical regulator of astrocyte function, with its disruption contributing to neurodevelopmental disorders. This study provides novel insights into the molecular pathways governing astrocyte differentiation and suggests EZH2 as a promising therapeutic target for gliomas and other CNS disorders.

摘要: Uterine fibroids (UFs) are the most common benign gynecologic tumours affecting women of reproductive age. This study aims to deepen the understanding of UFs complex aetiology through harnessing the power of 3D organoid models derived from human myometrial stem cells to emulate the in vivo behaviour of these tumours. Isolated SCs were cultured over 7 days under a defined culture system. Immunohistochemistry, Immunofluorescence, organoid stiffness, RNA Sequencing was conducted, and differential gene expression was assessed using RT-PCR. The derived organoids exhibited diverse populations of cells, including stem cells, smooth muscle, and fibroblasts. Excessive ECM deposition was shown via Collagen and Fibronectin expression. We confirmed that our organoids expressed oestrogen receptor in a pattern similar to that in their corresponding tissue, as well as responded to steroid hormone. Interestingly, we revealed significant racial disparities in ECM accumulation within organoids derived from different racial groups. This augmented ECM deposition is theorised to enhance tissue stiffness, as assessed using Young's modulus. Additionally, our research demonstrated significant decreases in fibrotic markers upon treatment with Vitamin D3 and Doxercalciferol. Furthermore, the pro-fibroid effects of environmental phthalates further elucidate the potential factors contributing to UF pathology. The 3D organoid model can serve as a robust platform to study the underlying molecular mechanisms of UFs, besides offering invaluable insights for potential therapeutic interventions.

摘要: Pigs are important agricultural animals whose growth rate and meat production performance are related to muscle development. Musculoskeletal embryonic nuclear protein 1 (MUSTN1) participates in various biological processes, including myogenesis and growth in animals, but the physiological functions and mechanisms of porcine MUSTN1 on muscle development are unclear; thus, we aimed to elucidate them. We found that MUSTN1 was highly expressed in the muscles of fast-growing pigs. Functionally, MUSTN1 promoted myoblast proliferation and differentiation. MUSTN1 knockout mice exhibited reduced muscle mass and fibre cross-sectional area, decreased exercise endurance, and delayed muscle regeneration. Small muscle protein X-linked (SMPX) was identified as an interacting protein of MUSTN1, and its promotion of myogenic differentiation depended on MUSTN1. Furthermore, MUSTN1 stabilised SMPX and maintained myofiber morphology. This study suggests that MUSTN1 is a critical regulator in the control of muscle development and regeneration and is a potential target for animal genetic improvement and the treatment of human muscle disease.

摘要: Mammalian olfactory epithelium (OE) undergoes consistent self-renewal throughout life. In OE homeostasis, globose basal cells (GBCs) contribute to the generation of olfactory sensory neurons (OSNs) to replace old ones. Chitinase-like 4 (Chil4), a chitinase-like protein expressed in supporting cells, plays a critical role in OE regeneration, while its role in tissue homeostasis is still elusive. Here, we found that Chil4 is upregulated in the aged OE. Deletion of Chil4 leads to a reduction in the number of GBCs and immature OSNs (iOSNs). Chil4(-/-) GBCs show attenuation in cell cycle progression and an aberrant expression pattern of cell-cycle-related genes such as Cdk1. Chil4 deletion causes loss of a specific subcluster of GAP43(+) iOSNs expressing Cebpb, Nqo1 and low level of mature OSN (mOSN) marker Stoml3 (iOSN_CeSt(L)Nq), potentially suggesting a transitional state between immature and mature neurons. Chil4 knockout induces inflammatory activation in Iba1(+) microglia (MG)-like cells in the OE. Chil4 downregulation in aged organoids reduced the number of mature sensory neurons, suggesting a necessary role of Chil4 in maintaining neuronal generation in the aged OE. Collectively, these observations reveal a previously unidentified function of Chil4, establishing the cellular mechanism underlying OE homeostasis.