Journal of Genetics and Genomics

Genome-wide association study of HBV-related hepatocellular carcinoma identifies a functional variant at the FAM114A1 locus

Hong-Ping Yu, Bang-De Xiang, et al.

doi: 10.1016/j.jgg.2025.11.003

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Abstract:
Liver cancer ranks sixth in cancer incidence and third in cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the primary histological subtype, and hepatitis B virus (HBV) carriers have a higher risk of HCC. Although several susceptibility loci for HCC have been identified in East Asian populations through genome-wide association studies (GWAS), the underlying biological mechanisms of this malignancy remain incompletely understood. Here, we conduct a two-stage GWAS including 2413 cases and 2794 HBV-positive controls from a high-incidence region in Southern China. The function of the susceptibility locus is investigated by bioinformatic and experimental approaches, supported by a xenograft model. We identify a 4p14 locus significantly associated with the risk of HCC (rs55718051, OR [95% CI] = 0.73 [0.67–0.80], P_meta = 9.14 × 10^-11), and 18q23 locus with borderline significance (rs12964643: OR [95% CI] = 0.75 [0.67–0.83], P_meta = 1.11 × 10^-7). Functional experiments indicate the role of rs55718051 in FAM114A1 expression regulation, possibly through interaction of FOXA1. Knockdown of FAM114A1 significantly enhances the oncogenic phenotypes in liver cancer cells, suggesting its potential tumor suppressor role. Our findings expand the understanding of HCC susceptibility and suggest FAM114A1 as a potential suppressor in HBV-related HCC carcinogenesis.

Key divisions and cell specification during embryo pattern formation require SMU1-mediated splicing of CAK genes in Arabidopsis

Xiaoyi Huang, Yue Liu, et al.

doi: 10.1016/j.jgg.2025.10.008

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Abstract:
Embryonic pattern formation and cell specification require precise cell division and cell cycle regulation. Splicing factors and the splicing of precursor mRNA (pre-mRNA) play significant roles in embryo development. However, how splicing factors control embryonic patterning via RNA splicing remains unclear. Here, we show that the mutation of SUPPRESSORS OF MEC-8 AND UNC-52 1 (SMU1), a conserved subunit of the spliceosomal B complex, causes compromised cell fate of the hypophysis and quiescent center (QC), failed embryonic root apical meristem (RAM) formation, as evidenced by altered WUSCHEL-RELATED HOMEOBOX 5 (WOX5) expression and perturbed auxin signaling. This results in smu1 embryo lethality. The splicing efficiency of three out of four CYCLIN-DEPENDENT KINASE ACTIVATOR (CAK) genes is decreased, leading to reduced protein levels in smu1 embryos. These CAK genes are required for hypophysis specification and embryonic RAM formation. SMU1 binds CAK transcripts in vitro and in vivo. Restoring the expression of either CAK gene partially rescues the defects in smu1 embryos, leading to the formation of QC-like cells, continued embryo development, and even the production of viable seeds. Our data suggest that SMU1 binds to CAK transcripts and promotes their splicing, enabling cell cycle progression to promote embryonic RAM formation.

Transcriptomic landscape of Marchantia polymorpha sexual organs at single-nucleus resolution

Yuying Zeng, Yuqing Cai, et al.

doi: 10.1016/j.jgg.2025.11.002

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Abstract:

Marchantia polymorpha, a model liverwort, provides a valuable system for investigating the evolution of plant sexual reproduction. To explore the cellular landscape of its reproductive structures, we generate a single-nucleus transcriptomic atlas of the antheridiophore, archegoniophore, and sporophyte. Using single-nucleus RNA sequencing (snRNA-seq), we capture over 30,000 high-quality nuclei and identify distinct cell populations. In the male organ, we characterize stages of spermatogenesis from early antheridium cells to mature sperm, revealing dynamic transcriptional programs including cell cycle regulation, chromatin remodelling, and calcium signalling. In the female organ, we define cell types including archegonial layers and secondary central cells. Sporophyte clusters are annotated as spores, elaters, capsule wall, foot, and seta cells, with transcriptional signatures related to structural support, stress response, and reproductive functions. Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells. Notably, foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways, serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte. This study provides a comprehensive cellular and molecular map of M. polymorpha reproductive organs and sporophyte, establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.

Epigenetic regulation of cilia stability and kidney development by the chromatin remodeling SWI/SNF complex in zebrafish

Xiaoyu Cheng, Qianshu Zhu, et al.

doi: 10.1016/j.jgg.2025.11.001

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Abstract:

Cilia are vital subcellular organelles whose assembly is regulated by master transcription factors, such as Foxj1 and Rfx. However, the mechanisms of epigenetic regulation over cilia stability remain largely unclear. Here, we investigate the epigenetic control by manipulating chromatin remodeling genes in zebrafish. We demonstrate that the depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex induces ciliopathy-like phenotypes in zebrafish embryos. Specifically, the loss of Actl6a, an essential component of the SWI/SNF complex, leads to cilia disassembly and cystic kidney defects, without affecting cilia motility. Our multi-omics analyses (RNA-seq, ATAC-seq, and FitCUT&RUN) consistently reveal that in Actl6a-depleted pronephros or embryos, a critical set of cilia genes, including the master regulators foxj1a and rfx2, exhibit concordant downregulation across the transcriptional level, chromatin accessibility, and SWI/SNF binding. Consistently, the depletion of foxj1a or rfx2 causes cilia assembly defects and cystic kidney formation in zebrafish. Furthermore, overexpression of either foxj1a or rfx2 mRNA substantially rescues the cystic kidney and cilia disassembly defects observed in actl6a^-/- mutant embryos. Collectively, these findings reveal that the SWI/SNF complex maintains cilia stability and kidney homeostasis by directly modulating the expression of the key ciliogenesis transcription factors foxj1a and rfx2.

ZmPRX38 is required for improving stalk strength and yield in maize

Xiaqing Wang, Tianyi Wang, et al.

doi: 10.1016/j.jgg.2025.10.009

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Abstract:
Stalk lodging is a major problem in maize production, usually causing significant yield losses due to weak stalk strength. Understanding the genetic basis of stalk strength is crucial for improving maize lodging resistance. In this study, we identify 31 quantitative trait loci (QTLs) related to maize stalk strength and clone ZmPRX38 (encoding peroxidase 38) responsible for a hotspot QTL region of stalk strength. ZmPRX38 is highly expressed in maize stalk during vegetative growth stage, and its protein is localized in the cell membrane, cytoplasm and apoplast. Knockout of ZmPRX38 decreases stalk strength and yield in maize, while overexpressing ZmPRX38 increases stalk strength and yield. ZmPRX38 in phenylpropanoid pathway is involved in the biosynthesis of guaiacyl lignin, p-hydroxy-phenyl lignin, and syringyl lignin. Additionally, we identify a favorable haplotype of ZmPRX38, which enhances stalk strength, containing 3 loci distributed in the 5’ untranslated region (UTR), exon 1, and 3’UTR of ZmPRX38, respectively. Although 91.46% of maize natural lines contain this favorable haplotype, most of the Huang-gai (HG) lines, a backbone maize germplasm, contain the unfavorable haplotypes. Therefore, targeted improvement of ZmPRX38 by editing unfavorable haplotypes may be an effective strategy for increasing maize stalk strength, thereby improving maize lodging resistance and yield.

Dual-target CRISPR-Cas12 diagnostics based on asymmetrically chemical-modified DNA probe

Xinge Wang, Yangcan Chen, et al.

doi: 10.1016/j.jgg.2025.10.007

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Abstract:
CRISPR-based nucleic acid detection technologies have revolutionized infectious disease detection and environmental monitoring by leveraging RNA–DNA complementarity to enable rapid, precise, and cost-effective detection of targets. However, achieving multitarget detection in one tube still presents challenges that necessitate further research. Here, we develop a nucleic acid detection module based on the CRISPR-Cas12i system. Importantly, we find that Cas12i and AapCas12b exhibit opposite trans-cleavage preferences for asymmetrically phosphorothioate-modified single-strand DNA probes, enabling the development of an effective dual-target nucleic acid detection platform by combining these two Cas12 nucleases in one tube. Moreover, this dual-target detection platform exhibits high specificity and sensitivity in genotyping the nucleic acid targets of human papillomavirus (HPV) 16 and HPV18, as well as Influenza A virus (FluA) and Respiratory syncytial virus. Notably, combined with loop-mediated isothermal amplification, this platform achieves high detection rates for clinical samples (18/18 FluA and 18/18 GAPDH internal reference detection rate). Taken together, these results can broaden the application of CRISPR-based Cas12 proteins for multi-target nucleic acid detection in one tube.