Cell Proliferation最新文献

Genomic imprinting, an epigenetic process resulting in parent-specific gene expression, is essential for normal development and growth. Disruption of imprinting leads to various developmental disorders and cancers, yet our understanding of the full repertoire of imprinted genes in humans remains incomplete. Here, we utilised androgenetic, parthenogenetic and biparental human embryonic stem cells and their neural derivatives to identify novel imprinted genes by analysing their methylome and transcriptome profiles. Our analysis revealed 12 novel putative imprinted genes distributed across four distinct loci, with six of them clustered in an uncharacterised imprinted region on chromosome 19. We identified potential imprinting control regions regulating this novel cluster, suggesting a coordinated regulatory mechanism. Notably, these imprinted genes are enriched in cancer-related pathways, with several showing isoform-specific imprinting patterns. Our analysis also revealed consistent DNA methylation aberrations in pluripotent stem cells at specific imprinted loci, highlighting potential epigenetic instability during culturing. These findings contribute to our understanding of genomic imprinting regulation in human development and highlight potential genomic regions for further investigation of imprinting-related disorders.

Retraction: T. Liu, X. Zhang, K. Sha, X. Liu, L. Zhang and B. Wang, "miR-709 Up-Regulated in Hepatocellular Carcinoma, Promotes Proliferation and Invasion by Targeting GPC5," Cell Proliferation 48, no. 3 (2015): 330-337, https://doi.org/10.1111/cpr.12181. The above article, published online on 27 March 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Qi Zhou; and John Wiley & Sons Ltd. The retraction has been agreed upon following the identification of duplicated elements between Figures 5c and 7c, which were reported to represent different experimental conditions. The authors provided some supporting data; however, it was insufficient to fully address the concerns. As a result, the editors have lost confidence in the reliability of the results. The authors did not respond when asked to agree to the final wording of the retraction.

Decreased sialic acid increases the adhesion of RBC membranes to immunoglobulins leading to an increased erythrocyte sedimentation rate (ESR). The increase in reactive oxygen species (ROS) damages the sialic acid glycosyl chains on the surface of RBC membrane proteins, causing the membrane proteins to be overexposed to the plasma environment due to the loss of sialic acid coverage. Immunoglobulins in plasma adhere to RBC membrane Band3 extracellularly exposed peptides through intermolecular interactions. The reduction of sialic acid causes a weakening of the RBC membrane negative charge barrier and the adhesion of immunoglobulins further destabilises the suspension of RBCs, resulting in a rapid addition of ESR to multiple myeloma.

Compared to classical drug screening, single-cell screening not only significantly enhances throughput but also provides richer transcriptional response information. In this study, we employed the high-throughput and high-sensitive single-nucleus sequencing platform, snHH-seq, to screen clinical drug combinations with anti-hepatocellular carcinoma (HCC) activity. Single-cell transcriptomics analysis revealed that the HY combination (HHT and YM155) exhibited the strongest suppression of tumour cell proliferation, a finding validated by both in vitro and in vivo functional assays. Further investigation suggested that HY triggers ferroptosis, as evidenced by rescue from cell death upon co-treatment with the ferroptosis inhibitor Fer-1. Subcluster analysis identified distinct tumour cell subclusters' responses to HY treatment. A gene regulatory network analysis highlighted JUN as a key regulator mediating proliferation inhibition, primarily active in the apoptotic cell subcluster. These findings illustrate how integrating high-throughput screening with mechanistic dissection can accelerate the discovery of targeted drug combination therapies, and offer a blueprint for precise interventions using pathway vulnerabilities and cellular heterogeneity in HCC.

Obstructive sleep apnea (OSA) is strongly associated with an increased risk of hypertension; however, the molecular mechanisms linking these two conditions remain incompletely understood. In this study, we identified phosphodiesterase 4B (PDE4B) as a key mediator in the development of OSA-related hypertension. Using integrated bioinformatics analysis and experimental validation, we found that PDE4B expression was significantly elevated in both cell and animal models of OSA combined with pulmonary hypertension. Functional studies demonstrated that PDE4B promotes pulmonary artery smooth muscle cell (PASMC) proliferation and migration, contributing to vascular remodelling. Mechanistically, we uncovered that lactate accumulation under hypoxic conditions induces histone lactylation at the PDE4B promoter, enhancing its transcriptional activity. Furthermore, PDE4B was shown to regulate the phosphorylation and nuclear translocation of FUS, which binds to the angiotensinogen (AGT) promoter and enhances AGT expression, thereby promoting pulmonary hypertension. These findings reveal a novel PDE4B-FUS-AGT signalling axis driven by epigenetic modifications in OSA-induced hypertension, offering potential therapeutic targets for patients with this comorbidity.

Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technologies, with the underlying molecular mechanisms still largely unknown. Here, we conducted proteomic profiling and analysed publicly available single-cell RNA sequencing data, revealing a marked decrease in lactate dehydrogenase A (LDHA) expression in RIF cases. While traditionally considered a metabolic byproduct, it is now recognised to play a role in signalling and epigenetic regulation. Utilising human endometrial organoids, we demonstrated that lactate enhances human endometrial receptivity by promoting epithelial-mesenchymal transition (EMT) and upregulating histone H3 lysine 18 lactylation (H3K18la). Further multi-omics analyses identified solute carrier family 7 member 11 (SLC7A11) as an H3K18la-regulated target. Functional assays confirmed that lactate-induced H3K18la upregulates SLC7A11, thereby driving EMT and cellular migration. Notably, using a blastoid-endometrial cell implantation model, we demonstrated that SLC7A11 promotes both blastoid adhesion and expansion, highlighting its critical role in embryo-endometrial interactions. Collectively, leveraging multiple organoid systems, including endometrial organoids and blastoid-endometrial cell implantation models, our findings reveal a novel lactate-H3K18la-SLC7A11 axis that orchestrates endometrial epithelial plasticity and receptivity. In addition, this study established a robust methodological framework for investigating implantation mechanisms.

Spinal cord injury (SCI) is a devastating condition with limited therapeutic options. Although neural stem cell (NSC) transplantation shows regenerative potential, its efficacy is constrained by the hostile post-injury microenvironment. Here, we employed untargeted metabolomics to investigate metabolic reprogramming induced by NSC-loaded multichannel collagen scaffolds in a rat SCI model. NSC transplantation significantly enhanced functional recovery and structural remodelling, concomitant with elevated neurogenesis and attenuated gliosis. Metabolomic profiling identified lysophosphatidylcholine 18:0 (LPC18:0) as a key NSC-derived metabolite. Mechanistically, LPC18:0 promoted the differentiation of endogenous NSCs into neurons via the GPR55/AKT/GSK3β signalling axis, as validated by receptor-specific inhibition. In vivo administration of LPC18:0 improved motor function, axonal regeneration and recruitment of immature neurons. These findings reveal a novel metabolic mechanism underlying NSC-based therapy, positioning LPC18:0/GPR55/AKT/GSK3β signalling as a therapeutic target for SCI recovery.

Mitochondrial quality control (MQC) impairment plays a central role in driving the pathogenesis of metabolism-associated steatotic liver disease (MASLD). Specifically, this is manifested as reduced mitophagy; increased mitochondrial fission and decreased fusion; and impaired mitochondrial biogenesis. Key pathological mechanisms of MASLD, such as hepatocyte apoptosis, pyroptosis, and ferroptosis, are activated under the influence of factors including free fatty acids (FFAs), oxidative stress, NLRP3 inflammasome activation, and gut microbiota imbalance. Meanwhile, the letter also lists novel potential therapeutic strategies targeting these pathways, including autophagy enhancers, mitochondrial dynamics regulators, biogenesis promoters, and ferroptosis inhibitors.

Periodontal regeneration requires coupled angiogenesis and osteogenesis, while current strategies to promote angiogenesis face limitations such as poor cytokine stability and safety concerns. Nanosilicates (nSi), as bioactive nanomaterials with potent properties, show promise for enhancing bone regeneration via osteogenic pathways. However, their pro-angiogenic potential and precise mechanisms, particularly within the periodontal microenvironment, remain poorly understood. This study addresses this knowledge void by introducing nSi into rat periodontal defects, revealing significantly enhanced vascular network formation and bone repair in vivo. Crucially, through intervention in relevant signalling pathways, this research provides the first evidence for the molecular mechanism underlying nSi-induced angiogenesis in endothelial cells. We demonstrate that nSi regulate microtubule homeostasis via the MAPK-mediated MAP4 signalling pathway, facilitating STAT3 nuclear translocation and ultimately promoting angiogenic differentiation. This mechanistic elucidation fills a critical gap in understanding the nSi-cytoskeleton-transcriptional regulation axis. These findings offer fundamental insights to guide the rational design and optimisation of nSi-based biomaterial systems for vascularised periodontal regeneration.