Journal of Genetics and Genomics

Mov10 mitigates hematopoietic stem cell exhaustion under stress by modulating the Camp-mediated inflammatory pathway

Changlin Zhen, Junbing Pan, et al.

doi: 10.1016/j.jgg.2026.05.012

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Abstract:
The integrity of hematopoietic stem cell (HSC) function is crucial for robust hematopoietic regeneration following stress. Inflammatory responses are pivotal drivers of HSC stress response, yet the precise modulation of inflammatory pathways remains incompletely defined. In this study, we identify the RNA helicase Mov10 as a negative regulator of stress-induced inflammatory pathways in HSC. Our study indicates that Mov10, which is critically required for HSC maintenance, is highly expressed in HSCs, and its loss adversely affects HSC fitness and survival during hematopoietic stress induced by bone marrow transplantation and irradiation (IR). Mechanistically, Mov10 mitigates excessive inflammatory activation to sustain HSC functional integrity during hematopoietic stress, primarily by enhancing the translation of CAMP, which inhibits the interaction between TNF-α and its receptor TNFR1 and suppresses NF-κB activation. Overall, our results imply that Mov10 plays a critical role in averting functional failure of hematopoiesis under stress, presenting viable paths for the therapeutic intervention of relevant diseases.

Multi-omics identification and verification of Dnajb14 as a modulator of retinal ganglion cell survival in glaucoma through ferroptosis

Yu Chen, Jie Wen, et al.

doi: 10.1016/j.jgg.2026.05.011

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Abstract:
Glaucoma is a leading cause of irreversible blindness and necessitates the identification of unreported therapeutic targets. Here, we report eight stable plasma protein targets for glaucoma, identified through a large-scale proteome-wide association study integrated with Mendelian randomization and colocalization analyses. Among these candidates, we show that the DnaJ heat shock protein family member B14 (DNAJB14) acts as a critical neuroprotective factor. Using single-cell and bulk transcriptomics, we demonstrate that Dnajb14 is characteristically expressed in retinal ganglion cells (RGCs) and that its abundance is inversely correlated with ferroptosis under ischemic stress. Furthermore, our results reveal that Dnajb14 preserve RGC survival and structural and functional integrity in multiple acute and chronic murine models. Mechanistically, Dnajb14 overexpression robustly alleviate ischemia-reperfusion-induced retinal injury, whereas targeted knockdown exacerbate lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Taken together, our findings highlight that Dnajb14 is a key regulator of RGC survival through inhibition of ferroptosis, thereby making it a promising therapeutic candidate for glaucoma treatment.

Original Research

Membrane depolarization drives tumor-suppressive cell competition via Hedgehog signaling activation

Kun Zhao, Dian Lv, et al.

doi: 10.1016/j.jgg.2026.05.010

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Abstract:
Tumor-suppressive cell competition (TSCC) is an evolutionarily conserved process that safeguards tissue integrity by selectively eliminating less-fit, precancerous cells. While bioelectric regulation via plasma membrane potential (V_m) is emerging as a key modulator of cellular fitness, its mechanistic role in TSCC remains underexplored. Here, we combine Drosophila genetics, single-cell RNA sequencing (scRNA-seq), and mammalian co-culture models to indicate that V_m depolarization acts as a critical driver of TSCC through Hedgehog (Hh) signaling. In Drosophila eye epithelia, scribble-deficient (scrib^−/−) “loser” clones exhibit mitochondrial respiratory chain defects, leading to reduced ATP synthesis and subsequent plasma membrane depolarization. This depolarization stabilizes Smoothened at the membrane, aberrantly activating Hedgehog signaling and triggering the elimination of scrib^−/− clones. Notably, we observe a striking mechanistic parallel in mammalian epithelia: Scrib-depleted Madin-Darby Canine Kidney (MDCK) cells similarly undergo V_m depolarization-dependent elimination associated with Hh pathway activation. Together, our work advances the understanding of bioelectricity in cancer surveillance and suggests that targeting membrane potential could offer a promising therapeutic strategy for cancer prevention by exploiting cell competition mechanisms.

Genetic dissection of cadmium accumulation in tea plants under nonphytotoxic field conditions

Shijie Luo, Xinwan Zhang, et al.

doi: 10.1016/j.jgg.2026.05.006

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Abstract:

Cadmium (Cd) accumulation in tea plants (Camellia sinensis) under chronic, nonphytotoxic field conditions poses a persistent food safety challenge; however, the genetic basis of this process remains uncharacterized. To dissect the genetic architecture of this trait, we quantify leaf Cd content and perform genome-wide association studies (GWAS) across 207 diverse tea accessions which have been cultivated for decades. Quantification analysis of Cd content reveals substantial natural variation in Cd content between young leaves (YL) and mature leaves (ML) under nonphytotoxic environment, with 38.2% of the 173 accessions with paired data intrinsically accumulating more Cd in YL than in ML. GWAS identify 112 quantitative trait loci associated with Cd accumulation. By further integrating the results of GWAS with Cd-responsive transcriptome profiling, we prioritize 14 high-confidence candidate genes. One of these candidate genes, CsHIPP6, which encodes a heavy metal-associated isoprenylated plant protein, is selected for further functional investigation. Heterologous expression in yeast and Arabidopsis demonstrates that CsHIPP6 enhances Cd tolerance and significantly reduces Cd accumulation. Our findings elucidate the genetic architecture underlying long-term Cd accumulation in perennial crops and highlight CsHIPP6 as a valuable target for breeding low-Cd tea cultivars to ensure beverage safety amidst rising environmental contamination.

The development and application of deep learning for stem cell research

Zhenfu Li, Wenjing Zhang, et al.

doi: 10.1016/j.jgg.2026.05.008

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Stem cells reside in specific microenvironments where they divide to maintain themselves and differentiate into functional cells that replace old, dead, or damaged cells to maintain tissue homeostasis. Some stem cells could also be cultured in vitro for self-renewal and directed differentiation towards specific lineages for both mechanistic interrogation and clinic investigation. A deeper understanding of the regulatory mechanisms underlying stem cell properties is essential for advancing their translational applications. Deep learning (DL), a branch of artificial intelligence, has been widely and deeply incorporated into different fields including biology. The application of DL in stem cells has revolutionized our research strategies and provided significant technical advantages. Here, we review the latest advances of the application of DL in analyzing bioimaging data and exploring large-scale genomics data in stem cells. We also summarize the limitations of current DL models and challenges of the application of these models in stem cell research.

Molecular basis of blade-pseudo-petiole-sheath axis patterning in Spodiopogon sagittifolius: roles of auxin signaling and lineage-specific regulators

Chao Xu, Yang Wang, et al.

doi: 10.1016/j.jgg.2026.05.007

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