RESUMEN
We have successfully derived a hiPSC line from PBMCs obtained from a 41-year-old infertile female. The patient's karyotype, as determined by Bionano OGM, revealed complex chromosomal rearrangements, including 46,XX,ins(1;15)(p13.3;q22.31q26.1),inv(2)(p22.1p16.3),t(2;14)(q34;q12). Specifically, the episomal plasmids encoding key reprogramming factors OCT4, sh-p53, SOX2, KLF4, L-MYC, and LIN28 were applied to generate the integration-free hiPSC line, which was designated as TONGJIi001-A. This line exhibits typical hiPSC morphology, expresses core pluripotency markers and presents the ability to differentiate into all three germ layers in vitro. Collectively, hiPSC TONGJIi001-A provides a valuable resource for investigating the mechanisms underlying chromosomal structural abnormalities associated with infertility.
RESUMEN
The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).
Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Manosa , Nanopartículas , Vacunas Virales , Animales , Nanopartículas/química , Virus de la Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/genética , Fiebre Porcina Africana/prevención & control , Fiebre Porcina Africana/inmunología , Ratones , Vacunas Virales/inmunología , Porcinos , Manosa/química , Células Dendríticas/inmunología , Lípidos/química , Desarrollo de Vacunas , ARN Mensajero/genética , ARN Mensajero/inmunología , Vacunas de ARNm , Femenino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , LiposomasRESUMEN
Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.
Asunto(s)
Implantación del Embrión , Regulación del Desarrollo de la Expresión Génica , Factor de Transcripción AP-2 , Factores de Transcripción , Animales , Femenino , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Implantación del Embrión/genética , Desarrollo Embrionario/genética , Redes Reguladoras de Genes , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción de Dominio TEA/metabolismo , Factor de Transcripción AP-2/metabolismo , Factor de Transcripción AP-2/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Tretinoina/metabolismoRESUMEN
Histone modifications play critical roles in regulating gene expression and present dynamic changes during early embryo development. However, how they are reprogrammed during human prenatal germline development has not yet been elucidated. Here, we map the genome-wide profiles of three key histone modifications in human primordial germ cells (hPGCs) from weeks 8 to 23 of gestation for the first time by performing ULI-NChIP-seq. Notably, H3K4me3 exhibits a canonical promoter-enriched pattern, though with relatively lower enrichment, and is positively correlated with gene expression in globally hypomethylated hPGCs. In addition, H3K27me3 presents very low enrichment but plays an important role in not only dynamically governing specific bivalent promoters but also impeding complete X chromosome reactivation in female hPGCs. Given the activation effects of both global DNA demethylation and H3K4me3 signals, repressive H3K9me3 and H3K27me3 marks are jointly responsible for the paradoxical regulation of demethylation-resistant regions in hPGCs. Collectively, our results provide a unique roadmap of three core histone modifications during hPGC development, which helps to elucidate the architecture of germ cell reprogramming in an extremely hypomethylated DNA environment.
