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PubMed2005

Transcriptional reprogramming and backup between duplicate genes: is it a genomewide phenomenon?

Deleting a duplicate gene often results in a less severe phenotype than deleting a singleton gene, a phenomenon commonly attributed to functional compensation among duplicates. However, duplicate genes rapidly diverge in expression patterns after duplication, making functional compensation less probable for ancient duplicates. Case studies suggested that a gene may provide compensation by altering its expression upon removal of its duplicate copy. On the basis of this observation and a genomic analysis, it was recently proposed that transcriptional reprogramming and backup among duplicates is a genomewide phenomenon in the yeast Saccharomyces cerevisiae. Here we reanalyze the yeast data and show that the high dispensability of duplicate genes with low expression similarity is a consequence of expression similarity and gene dispensability, each being correlated with a third factor, the number of protein interactions per gene. There is little evidence supporting widespread functional compensation of divergently expressed duplicate genes by transcriptional reprogramming.

Genes, Duplicate↗

PubMed2006

The role of exogenous fibroblast growth factor-2 on the reprogramming of primordial germ cells into pluripotent stem cells.

The germ cell lineage is a specified cell population that passes through a series of differentiation steps before giving rise, eventually, to either eggs or sperm. We have investigated the manner in which primordial germ cells (PGCs) are reprogrammed in vitro to form pluripotent stem cells in response to exogenous fibroblast growth factor-2 (FGF-2). The response is dependent on time of exposure and concentration of FGF-2. PGCs isolated in culture show a motile phenotype and lose any expression of a characteristic germ cell marker, mouse vasa homolog. Subsequently, some but not all of the cells show further changes of phenotype, accompanied by changes in expression of endogenous FGF-2 and up-regulation of its receptor, fibroblast growth factor receptor-3, in the nucleus. We propose that it is from this reprogrammed component of the now heterogeneous PGC population that pluripotent stem cells arise.

Animals↗

PubMed2003

Reprogramming immune responses: enabling cellular therapies and regenerative medicine.

Recent advances in cellular therapies have led to the emergence of a multidisciplinary scientific approach to developing therapeutics for a wide variety of diseases and genetic disorders. Although most cell-based therapies currently consist of heterogeneous cell populations, it is anticipated that the standard of care will eventually be well-characterized stem cell lines that can be modified to meet the individual needs of the patient. Many challenges have to be overcome, however, before such "designer cells" can become a clinical reality. One of the major hurdles will be to prevent immune rejection of the therapeutic cells. A patient's immune system may react to genetically modified or allogeneic cells as foreign, leading to their destruction. We propose that specific reprogramming of the immune system to accept cellular therapies can be accomplished by establishing hematopoietic chimerism. Successful engraftment of hematopoietic stem cells (HSCs), which have the same origin as those cells intended for therapeutic use, should lead to a re-education of the immune system so that the donor cells are recognized as self and will not be rejected. Developing safe, nontoxic protocols for reprogramming the immune system is critical to the success of this approach. Two major requirements exist for achieving stable HSC engraftment: (A) depletion or displacement of host stem cells, and (B) adequate immune suppression. Available data indicate that an agent such as busulfan is effective in depleting stem cells and that immune suppression can be accomplished with monoclonal antibodies that specifically target immune-reactive cells in the periphery.

Animals↗

PubMed2004

Nuclei of embryonic stem cells reprogram somatic cells.

The restricted potential of a differentiated cell can be reverted back to a pluripotent state by cell fusion; totipotency can even be regained after somatic cell nuclear transfer. To identify factors involved in resetting the genetic program of a differentiated cell, we fused embryonic stem cells (ESCs) with neurosphere cells (NSCs). The fusion activated Oct4, a gene essential for pluripotency, in NSCs. To further identify whether cytoplasmic or nuclear factors are responsible for its reactivation, we fused either karyoplasts or cytoplasts of ESCs with NSCs. Our results show that ESC karyoplasts could induce Oct4 expression in the somatic genome, but cytoplasts lacked this ability. In addition, mitomycin C-treated ESCs, although incapable of DNA replication and cell division, could reprogram 5-azacytidine-treated NSCs. We therefore conclude that the Oct4 reprogramming capacity resides in the ESC karyoplast and that gene reactivation is independent of DNA replication and cell division.

Animals↗

PubMed2026

Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs), represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have shown remarkable efficacy in non-small cell lung cancer (NSCLC); however, many patients still develop resistance to immunotherapy. Although small cell lung cancer (SCLC) is also an important histological type of lung cancer, NSCLC accounts for the majority of lung cancer cases. Current research on ICI development, first-line treatment efficacy, and the mechanisms of lipid metabolism in tumor-associated macrophages (TAMs) is predominantly focused on NSCLC. In patients with advanced NSCLC, objective response rates (ORRs) with PD-1/PD-L1 inhibitor monotherapy remain limited. Only in patients with high PD-L1 expression [tumor proportion score (TPS) ≥50%] and without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements does the ORR increase to approximately 40-45%. TAMs are a key component of the immunosuppressive tumor microenvironment (TME). Lipid metabolic reprogramming profoundly influences the functional and transcriptional features of TAMs. This review aims to integrate relevant evidence, elucidate how TAM lipid metabolism promotes immunosuppression and resistance to ICIs, and outline potential therapeutic strategies. METHODS: We searched PubMed/MEDLINE, Web of Science, and Scopus for publications up to June 2026 using terms combining lung cancer, TAMs, lipid metabolism, and immune checkpoint blockade/resistance. Mechanistic, translational, and clinically relevant studies were selected by author consensus. KEY CONTENT AND FINDINGS: Lipid uptake, de novo lipogenesis, fatty acid oxidation (FAO), cholesterol remodeling, and eicosanoid metabolism are not independent processes in TAMs. Lipid metabolic reprogramming in TAMs ultimately suppresses type I interferon (IFN-I) signaling, upregulates PD-L1 expression, and impairs the function of CD8+ T cells with stem-like features, thereby establishing an immunosuppressive TME and leading to resistance to ICIs. In lung cancer, hypoxia, high lactate levels, and tobacco exposure further shape the lipid phenotype of TAMs, such as lipid raft enrichment and lipid-laden macrophage subsets like SPP1+ macrophages. Different driver genomic backgrounds differentially impact tumor cell-intrinsic metabolism and the lipid metabolic programs of myeloid cells. In preclinical models, interventions targeting these metabolic axes, including TAM-directed delivery systems, have demonstrated potential therapeutic benefit when combined with anti-PD-1/PD-L1 therapy. CONCLUSIONS: Targeting TAM lipid metabolism to convert immunologically cold tumors into more inflamed, ICI-responsive tumors is a promising strategy to overcome resistance in NSCLC. Identification of predictive biomarkers of therapeutic response and development of cell-selective drug delivery systems come to be major challenges.

Non-small cell lung cancer (NSCLC)↗

PubMed2000

Reprogramming erythroleuekmia cells to terminal differentiation and terminal cell division.

In vitro differentiation of murine erythroleuekemia cells recapitulates many aspects of the erythroid terminal differentiation program, including hemoglobin synthesis and proliferation arrest. It also provides an opportunity to study the changes occurring during reprogramming of tumor cells into their normal differentiation program. This review is focused on the recent progress made in understanding the key events occurring during the reprogramming of erythroleukemia cells. We discuss the contributions of PU.1 to the block to terminal differentiation exhibited by the erythroleukemia cells as well as the role of GATA-1 in restoring normal differentiation. We also discuss the role of certain cell cycle regulators in the decision to resume normal differentiation and in the resulting terminal cell divisions and arrest.

Animals↗

PubMed2026

Rapid transcriptional reprogramming underlies Fusarium wilt resistance in strawberry: insights from comparative physiological and transcriptomic analyses.

INTRODUCTION: Fusarium wilt caused by Fusarium oxysporum f. sp. fragariae (Fof) severely constrains strawberry production, yet the underlying resistance mechanisms remain unclear. METHODS: A total of 64 strawberry germplasm accessions were evaluated for Fusarium wilt resistance. Integrated physiological and transcriptomic analyses were subsequently performed using the highly resistant cultivar 'Akihime' (ZJ) and the highly susceptible cultivar 'Ning Yu' (NY). RESULTS: Resistant resources were abundant, particularly among wild strawberry accessions. Compared with NY, ZJ exhibited higher soluble sugar accumulation, reduced oxidative damage, and increased peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities. Transcriptomic analyses revealed distinct temporal response patterns: ZJ underwent rapid and extensive transcriptional reprogramming at 24 h post-inoculation, whereas NY showed limited early responses but pronounced changes at 120 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that the early response of ZJ was mainly associated with stress-related processes, jasmonic acid-mediated signaling, transmembrane transport, plant-pathogen interaction, mitogen-activated protein kinase (MAPK) signaling, glutathione metabolism, plant hormone signal transduction, and secondary metabolism. Quantitative real-time polymerase chain reaction (qRT-PCR) validation supported the RNA-seq results and identified candidate genes associated with pathogen recognition, signaling, redox regulation, and protein homeostasis. DISCUSSION: These results indicate that rapid early immune activation and coordinated physiological and metabolic reprogramming are closely associated with strawberry resistance to Fof and provide useful germplasm and candidate genes for future functional validation and resistance breeding.

Fusarium oxysporum f. sp. fragariae↗

PubMed2002

Full-screen ultrafast video modes over-clocked by simple VESA routines and registers reprogramming under MS-DOS.

Fast full-screen presentation of stimuli is necessary in psychological research. Although Spitczok von Brisinski (1994) introduced a method that achieved ultrafast display by reprogramming the registers, he could not produce an acceptable full-screen display. In this report, the author introduces a new method combining VESA routine calling with registers reprogramming that can yield a display at 640 x 480 resolution, with a refresh rate of about 150 Hz.

Computer Graphics↗

PubMed2003

[Nuclear transfer and reprogramming mechanism].

It is confident that mammalian somatic cell and embryonic stem cell can form whole individuals if they are transferred to enucleated oocytes at M phase. However, a large proportion of clones were stillborn or died within several months due to various reasons. Morphological abnormalities have also been observed in clones. The exact reasons for such abnormalities are not clear, but genetic or epigenetic modification in donor cells and insufficient reprogramming of nuclei due to improper nuclear transfer technique are considered. In this review, we discuss the present status of animal cloning and reprogramming mechanism of nuclei.

Animals↗

PubMed2003

[Isolation and identification of reprogramming genes related to the development of the rabbit reconstructed embryos].

By the method of single preimplantation embryos differential display polymerase chain reaction (SPEDDRT-PCR), 25 reprogramming cDNA fragments were obtained from single 2-cell, 8-cell embryos and blastula. After cloning and sequencing, five of them were identified by reverse-Northern and characterized with stage-specific expression during reconstructed embryo development. This results will help to isolate full length reprogramming genes and study their function during embryonic development.

Animals↗

PubMed1993

Reprogramming of nucleolar gene expression during the acclimatization of the carp.

During seasonal acclimatization of eurythermal fish, the nucleolus of the hepatocyte undergoes ultrastructural reprogramming. In winter acclimatized carp, the nucleolar components are segregated, a condition that suggests a decreased transcription of rRNA. The same nucleolar reorganization was observed when pituitary cells from winter- and summer-acclimatized carp were examined. In situ analyses of nucleolar RNA revealed a marked lowering of RNA content in the segregated nucleoli. Accordingly, in vitro synthesis of RNA was shown to be significantly lower in pituitary tissue from cold-acclimatized fish where precursor accumulated. Conversely, in pituitary tissue from summer-adapted fish the rate and extent of synthesis and of rRNA processing was notably higher. The involvement of pre-rRNA processing events during seasonal acclimatization was corroborated by the strong differences of U3 RNA content detected by in situ hybridization in pituitary cells from summer- and winter-fish. When RNA polymerase I activity from both acclimatized states were assayed, no differences were detected. Thus, it appears that in fish RNA polymerase I itself does not play an important role in the control of nucleolar gene expression and the nucleolar gene expression reprogramming that the seasonal rearrangement represents might involve, among the many nucleolar-specific proteins, transcription factors.

Acclimatization↗

PubMed2026

Oxidative stress-driven epigenetic reprogramming of immune cells in COPD: from epitranscriptomic and metabolic crosstalk to treatable traits.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome characterized by persistent oxidative stress and maladaptive immune responses, rather than a single disease entity. Oxidative stress not only damages lung tissue but also reprograms immune cells through both classical epigenetic mechanisms (DNA methylation, histone modifications) and epitranscriptomic regulation (m6A RNA methylation), shaping disease endotypes and treatment resistance. This review presents an integrated framework in which redox signals dynamically reshape the epigenetic and epitranscriptomic landscape, thereby locking immune cells into pathogenic states. Metabolic intermediates (S-adenosylmethionine, α-ketoglutarate, succinate, NAD+) serve as critical nodes that connect immunometabolism to both classical epigenetic enzymes and the m6A machinery, thereby linking redox status to RNA fate. Using NETosis as a paradigm, we illustrate how oxidative-epigenetic-metabolic loops sustain neutrophilic inflammation and resolution failure. Finally, we outline a treatable traits framework that integrates these mechanistic insights into precision combination therapies. This conceptual roadmap aims to shift COPD management from symptom control toward durable, mechanism-driven disease modification.

Humans↗

PubMed2026

CHCHD10 Mitigates Alzheimer's Disease-Related Phenotypes in Association With Epigenetic Remodeling in Directly Reprogrammed Neurons.

Mitochondrial dysfunction and chromatin dysregulation are interconnected contributors to neuronal vulnerability in Alzheimer's disease (AD), yet the molecular mechanisms linking these processes remain poorly understood. CHCHD10, a mitochondrial intermembrane space protein, has been implicated in neurodegenerative disorders, but its role in AD has not been defined. Here, we identify CHCHD10 as a previously unrecognized modulator of neuronal epigenomic stability in AD. Using direct fibroblast-to-neuron reprogramming, which preserves patient-specific epigenetic signatures, we show that AD neurons recapitulate genome-wide hypomethylation patterns observed in postmortem AD cortex. CHCHD10 expression is significantly reduced in AD neurons and across multiple human brain datasets, including single-cell and bulk RNA sequencing, proteomics, and human cortical tissue analyses. Restoration of CHCHD10 in AD neurons reduces amyloid-β and insoluble tau accumulation while reversing AD-associated differentially methylated regions across CpG islands, promoters, and regulatory elements. CHCHD10-responsive methylation changes overlap with those observed in human AD brain regions and colocalize with significant AD loci and cortex-specific eQTL loci, including MAPT and ABCA7. Finally, we identify KATNAL2 as a CHCHD10-responsive effector whose loss enhances tau phosphorylation and seeding, whereas its restoration mitigates tau pathology. Together, these findings support a CHCHD10-associated neuroprotective pathway linking mitochondrial dysfunction, epigenomic instability, and tau pathology in AD.

Humans↗

PubMed2025

DNA Methylation Analysis by Bisulfite Pyrosequencing of Mouse Embryonic Fibroblasts with Reprogramming Enhanced by Thyroid Hormones.

DNA methylation is a widely studied epigenetic mark which in mammals involves the incorporation of a methyl group to the fifth carbon of cytosines, mainly those belonging to CpG dinucleotides. It has been linked to context-dependent regulatory functions ranging from gene and repetitive DNA silencing to gene body transcriptional activity. Because of its important roles during embryonic development and cell differentiation, DNA methylation can be used to track cell reprogramming by measuring the methylation levels of pluripotency-associated factors. In this scenario, bisulfite pyrosequencing is a simple, robust, and widely used technique which allows for the quantification of DNA methylation levels at small, specific regions of the genome. It involves the amplification and biotin tagging of bisulfite-converted DNA. Single amplified strands are then purified using streptavidin and finally pyrosequenced using a sequencing primer. Thus, it is an ideal method for the quantitative profiling of specific genomic regions, with applications ranging from biomarker discovery and epigenetic clock tracking to omic validation studies.

Animals↗

PubMed2026

Multi-omics integration uncovers epigenetic control of metabolic reprogramming in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen, progesterone, and HER2 receptors, limiting effective targeted therapies. Increasing evidence suggests that metabolic reprogramming, a hallmark of TNBC progression, is driven by underlying epigenetic mechanisms such as DNA methylation. The represented study performed an integrative analysis of transcriptomic (RNA-seq) and methylome data to uncover the metabolic-epigenetic interplay in TNBC. Differential gene expression analysis using DESeq2 revealed significant dysregulation of key metabolic genes, including upregulation of genes encoding glycolytic and serine biosynthesis enzymes and downregulation of metabolic tumor suppressors. Genome-wide methylation profiling identified extensive cytosine-phosphate-guanine (CpG) hypermethylation events associated with transcriptional repression, particularly in promoter regions. Integrative analysis pinpointed a subset of metabolism-related genes exhibiting both differential expression and methylation, such as FBP1, RASSF1A, and PHGDH. Pathway enrichment analysis highlighted aberrations in glycolysis/gluconeogenesis, fatty acid metabolism, and one-carbon pathways (adjusted p < 0.01). Importantly, TNBC patients with hypermethylated metabolic gene signatures displayed significantly shorter overall survival (log-rank p < 0.05). These findings reveal that DNA methylation-driven metabolic dysregulation contributes to TNBC aggressiveness and may provide novel biomarkers and therapeutic targets at the metabolic-epigenetic interface.

Humans↗

PubMed2026

Prophylactic Inhaled Pattern Recognition Receptor Agonists Reprogram Lung Epithelial Response and Prevent Type 2 Allergic Inflammation.

Prophylactic inhalation of the synergistic agents ODN M362 and Pam2CSK4 ("Pam2ODN") protects mice against allergic lung disease, including allergic inflammation caused by house dust mite (HDM). By preventing sensitization, Pam2ODN reduces HDM-induced eosinophilic and lymphocytic inflammation. How Pam2ODN affects interactions among lung epithelial cells, dendritic cells, and T cells to prevent eosinophilic lung inflammation remains unclear. In the present study, we show that a single inhaled dose of Pam2ODN before HDM sensitization reduces airway Th2 polarization without affecting Th1 or Treg responses. Furthermore, Pam2ODN pretreatment inhibits the recruitment of lung monocyte-derived dendritic cells (moDCs) and conventional Type 2 dendritic cells (DC2s), while preventing the HDM-induced decrease in conventional Type 1 dendritic cells (DC1s). Bulk RNA-seq of the whole lung reveals that Pam2ODN pretreatment restricts the expression of proinflammatory transcripts induced by HDM sensitization. This tolerogenic effect is also reflected at the single-cell level in lung epithelial cells, where proinflammatory transcripts, pathways, and chromatin accessibility are inhibited. These results indicate that Pam2ODN reprograms lung epithelial cells to attenuate allergen-induced Th2-promoting cytokines and DCs while maintaining the population of protective DC1s. These findings suggest a strategy to mitigate chronic allergic lung diseases.

Animals↗

PubMed2026

Phytoplasma-plant interactions: effector-mediated host reprogramming, hormonal crosstalk, metabolic alterations and plant-mediated vector manipulation.

Phytoplasmas are wall-less, phloem-restricted bacterial pathogens that infect over 1,000 plant species, causing substantial losses in agriculture, horticulture, and forestry worldwide. Despite their reduced genomes and limited metabolic autonomy, these obligate parasites colonize diverse hosts through secreted effector proteins that extensively reprogram plant development, metabolism, immune signalling, and vector interactions. Advances in genomics, transcriptomics, proteomics, metabolomics, and functional studies have substantially clarified the molecular basis of phytoplasma pathogenicity and symptom development. This review synthesizes current understanding of phytoplasma-plant interactions, covering phytoplasma biology, genome evolution, and the infection cycle across plant and insect vector hosts. We examine the molecular functions of key effectors, SAP11, SAP54/PHYL1, SAP05, TENGU, SWP1, and recently identified virulence factors, focusing on how they target host transcription factors, phytohormone networks, protein degradation pathways, and immune responses to promote colonization and disease progression. We further discuss how phytoplasma infection disrupts phytohormone signalling, primary and secondary metabolism, and developmental programs to produce characteristic disease symptoms, with particular attention to pathogen-induced changes in host volatiles and nutritional quality that alter vector behaviour and enhance transmission. Finally, we summarize insights from multi-omics studies and emerging management strategies, including CRISPR-based genome editing, RNAi, rapid molecular diagnostics, resistant cultivars, microbiome-based approaches, and sustainable vector control, and highlight key knowledge gaps and priorities for developing effective, environmentally sustainable phytoplasma disease management.

Phytoplasma↗

PubMed2026

Lactylome Reprogramming Mediates Therapeutic Response and Adaptation to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) exhibits high prevalence in China and poor prognosis despite neoadjuvant chemotherapy (NACT), with significant chemoresistance development. Tumor-associated metabolic reprogramming and NACT-induced cellular stress promote lactate accumulation, which serves as a precursor for lysine lactylation (Kla), a post-translational modification potentially regulating cancer progression. We hypothesized that systematic characterization of the lactylome in response to NACT could reveal critical molecular mechanisms underlying treatment and identify new therapeutic vulnerabilities in ESCC. Herein, through comprehensive proteomic and lactylome profiling of tumor and adjacent normal adjacent tissues from 31 ESCC patients (with or without NACT treatment), we identified 8281 proteins and 1836 Kla sites across 62 samples. NACT induced substantial lactylome alterations with 307 differentially expressed Kla sites predominantly in nonhistone proteins involved in DNA damage response and metabolic pathways. Our data revealed that while NACT-induced suppression of energy metabolism, coupled with upregulated 3-hydroxy-3-methylglutaryl reductase degradation 1 complex expression, may exert potential proapoptotic effects, the activation of ribosome biogenesis and increased nucleoprotein lactylation triggered tumor-protective mechanisms. Mechanistically, we demonstrated that DNA damage and elevated lactate levels induced poly(ADP-ribose) polymerase 1 K654 lactylation, enhancing its enzymatic activity and augmenting poly(ADP-ribosyl)ation of downstream targets, potentially playing a pivotal role in chemotherapy resistance-associated pathways. This comprehensive tissue-level landscape of Kla dynamics in ESCC response to chemotherapy establishes Kla as a critical regulatory mechanism in treatment response, potentially offering novel therapeutic targets and predictive biomarkers for personalized treatment strategies.

Humans↗