Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “reprogramming”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2006

Are the elderly able to appropriately reprogram their actions?

Movement reprogramming in a task requiring timing accuracy was investigated in young and elderly individuals. The task consisted of manually hitting a hemiball in synchrony with the arrival of a moving light stimulus running through an electronic trackway. Movement reprogramming was required by unexpectedly changing the regular stimulus velocity at different moments before the due time of arrival at the interception position. Such changes produced times after velocity decrease (TAVD) between 150 ms and 750 ms, representing the periods of time available for generation of new movement timing specifications. Effect of probability of stimulus velocity change was investigated by comparing the conditions of 25% and 50% of chance of velocity decrease. Analysis of performance in conditions of velocity decrease showed an enlargement of temporal error as a function of longer TAVDs up to 300-375 ms. In conditions in which TAVDs were longer than 375 ms young participants showed a progressive improvement of accuracy over time, while the elderly were unable to improve their performance even for a TAVD of 750 ms. A trend toward a more efficient reprogramming with reduced uncertainty was observed only in the young. These results indicate that movement reprogramming is a continuous process in young individuals, but it is impaired in the elderly, preventing an appropriate reorganization of the action.

Adolescent↗
PubMed2001

Nuclear cloning and epigenetic reprogramming of the genome.

Cloning of mammals by nuclear transfer (NT) results in gestational or neonatal failure with at most a few percent of manipulated embryos resulting in live births. Many of those that survive to term succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Cloned embryos derived from donors, such as embryonic stem cells, that may require little or no reprogramming of early developmental genes develop substantially better beyond implantation than NT clones derived from somatic cells. Although recent experiments have demonstrated normal reprogramming of telomere length and X chromosome inactivation, epigenetic information established during gametogenesis, such as gametic imprints, cannot be restored after nuclear transfer. Survival of cloned animals to birth and beyond, despite substantial transcriptional dysregulation, is consistent with mammalian development being rather tolerant to epigenetic abnormalities, with lethality resulting only beyond a threshold of faulty gene reprogramming encompassing multiple loci.

Animals↗
PubMed2006

Nuclear reprogramming of somatic nucleus hybridized with embryonic stem cells by electrofusion.

Cell fusion is a powerful tool for understanding the molecular mechanisms of epigenetic reprogramming. In hybrid cells of somatic cells and pluripotential stem cells, including embryonic stem (ES) and embryonic germ cells, somatic nuclei acquire pluripotential competence. ES and embryonic germ cells retain intrinsic trans activity to induce epigenetic reprogramming. For generating hybrid cells, we have used the technique of electrofusion. Electrofusion is a highly effective, reproducible, and biomedically safe in vitro system. For successful cell fusion, two sequential steps of electric pulse stimulation are required for the alignment (pearl chain formation) of two different types of cells between electrodes in response to alternating current stimulation and for the fusion of cytoplasmic membranes by direct current stimulation. Optimal conditions for electrofusion with a pulse generator are introduced for ES and somatic cell fusion. Topics in the field of stem cell research include the successful production of cloned animals via the epigenetic reprogramming of somatic cells and contribution of spontaneous cell fusion to generating intrinsic plasticity of tissue stem cells. Cell fusion technology may make important contributions to the fields of epigenetic reprogramming and regenerative medicine.

Animals↗
PubMed1997

Nuclear transfer and reprogramming.

Nuclear transfer techniques for mammalian embryos have been developed in the last decade. Embryonic nuclei from advanced stages of preimplantation development can be fully reprogrammed and the totipotency is restored when nuclei are transferred into ooplasts. Transfer of nuclei after gene expression from the embryonic genome has started does not appear to restrict the reprogramming of these nuclei. The principles of nuclear transfer are outlined with respect to nuclear remodelling, nucleocytoplasmic interactions and effects of the cell cycle. However, the molecular mechanisms involved in reprogramming donor nuclei remain unknown. It is proposed that epigenetic DNA modification, such as DNA methylation that regulates gene expression, is related to the reprogramming of transplanted nuclei.

Animals↗
PubMed2005

Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones: distinct developmental potentials in different culture environments.

A prevailing view of cloning by somatic-cell nuclear transfer is that reprogramming of gene expression occurs during the first few hours after injection of the nucleus into an oocyte, that the process is stochastic, and that the type of reprogramming needed for cloning success is foreign and unlikely to be readily achieved in the ooplasm. Here, we present evidence that the release of reprogramming capacity is contingent on the culture environment of the clone while the contribution of aneuploidy to altered gene expression is marginal. In particular, the rate of blastocyst formation in clones and the regional distribution of mRNA for the pluripotent stem cell marker Oct4 in clonal blastocysts was highly dependent on the culture environment after cumulus cell nuclear transfer, unlike that in genetically equivalent zygotes. Epigenetic modifications of genetically identical somatic nuclei continue after the first cell division of the clones and are amenable to a degree of experimental control, and their development to the blastocyst stage and appropriate expression of Oct4 predict further outcome, such as derivation of embryonic stem (ES) cells, but not fetal development. This observation indicates that development to the blastocyst stage is not equivalent to full reprogramming and lends support to the novel concept that ES cells are not the equivalent of the inner cell mass, hence the discrepancy between ES cell derivability and fetal development of clones.

Animals↗
PubMed2005

Nuclear cloning, epigenetic reprogramming and cellular differentiation.

The full-term development of sheep, cows, goats, pigs and mice has been achieved through the transfer of somatic cell nuclei into enucleated oocytes. Despite these successes, mammalian cloning remains an inefficient process, with a preponderance of reconstructed embryos failing at early- to mid-gestation stages of development. The small percentage of conceptuses that survive to term are characterized by a high mortality rate and frequently display grossly increased placental and birth weights. It is likely that inappropriate expression of key developmental genes may contribute to lethality of cloned embryos. One of the most interesting issues of nuclear cloning is the question of genomic reprogramming, i.e. whether successful cloning requires the resetting of epigenetic modifications which are characteristic of the adult donor nucleus. Processes such as X-inactivation and genomic imprinting are known to depend on epigenetic modifications of the genome. The classical nuclear transfer experiments with frogs have suggested that the source of the donor nucleus affects the phenotype of the clone. We have, using expression profiling, compared gene expression in clones derived from embryonic stem (ES) cells and from somatic donor cell nuclei and find substantial gene dysregulation. Our results suggest that faulty reprogramming is caused by the nuclear cloning procedure itself. In addition, the type of donor nucleus contributes to the abnormal expression pattern seen in cloned animals. One of the major unresolved issues has been whether nuclei of terminally differentiated cells can be reprogrammed by transfer into the oocyte. To address this question we have derived monoclonal mice from B and T cells and used the genetic rearrangements of the immunoglobulin and T cell receptor genes to retrospectively verify the differentiation state of the donor nucleus. Finally, we discuss our recent studies on the reprogramming of nuclei from terminally differentiated neurons and from cancer cells.

Animals↗
PubMed2025

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗
PubMed2026

HDGF induces inflammatory cancer-associated fibroblast formation through ENO1-mediated glycolytic reprogramming in esophageal squamous-cell carcinoma.

Inflammatory cancer-associated fibroblasts (iCAFs) are a highly plastic stromal population that critically shape tumor progression, immunosuppression, and therapeutic response in esophageal squamous-cell carcinoma (ESCC). Epithelial-intrinsic programs are increasingly recognized as key determinants of fibroblast reprogramming within the tumor microenvironment, yet the underlying mechanisms remain incompletely understood. Here, we identified hepatoma-derived growth factor (HDGF) as a pivotal epithelial-intrinsic regulator that drives iCAF formation in ESCC. Mechanistically, nuclear HDGF functioned as a transcriptional activator by directly binding the ENO1 promoter, thereby upregulating the expression of the glycolytic enzyme enolase 1, enhancing aerobic glycolysis, and promoting lactate secretion from tumor cells. Tumor-derived lactate was subsequently taken up by CAFs and induced histone H4 lysine 12 lactylation (H4K12la), which epigenetically activated NF-κB signaling and promoted iCAF formation. Functionally, HDGF-induced iCAFs promoted tumor progression through activation of the IL-6/JAK1/STAT3 axis and established an immunosuppressive microenvironment characterized by increased recruitment of regulatory T cells and reduced infiltration of CD8+ T cells, thereby facilitating immune evasion. Therapeutically, blockade of ENO1 effectively disrupted the glycolysis-lactylation cascade, markedly suppressing tumor growth and iCAF formation in vivo. Moreover, ENO1 inhibition reprogrammed the immunosuppressive tumor microenvironment and significantly enhanced the efficacy of anti-PD-1 therapy. Collectively, our findings reveal an HDGF/ENO1/H4K12la/iCAF axis that links tumor metabolic reprogramming, stromal inflammatory activation, and immunosuppression in ESCC, identifying this axis as a promising therapeutic target for overcoming immunotherapy resistance.

Phosphopyruvate Hydratase↗
PubMed2006

Premature chromosome condensation is not essential for nuclear reprogramming in bovine somatic cell nuclear transfer.

Premature chromosome condensation (PCC) was believed to promote nuclear reprogramming and to facilitate cloning by somatic cell nuclear transfer (NT) in mammalian species. However, it is still uncertain whether PCC is necessary for the successful reprogramming of an introduced donor nucleus in cattle. In the present study, fused NT embryos were subjected to immediate activation (IA, simultaneous fusion and activation), delayed activation (DA, activation applied 4 h postfusion), and IA with aged oocytes (IAA, activation at the same oocyte age as group DA). The morphologic changes, such as nuclear swelling, the occurrence of PCC, and microtubule/aster formation, were analyzed in detail by laser-scanning confocal microscopy. When embryos were subjected to IA in both IA and IAA groups, the introduced nucleus gradually became swollen, and a pronuclear-like structure formed within the oocyte, but PCC was not observed. In contrast, delaying embryo activation resulted in 46.5%-91.2% of NT embryos exhibiting PCC. This PCC was observed beginning at 4 h postcell fusion and was shown as one, two, or multiple chromosomal complexes. Subsequently, a diversity of pronuclear-like structures existed in NT embryos, characterized as single, double, and multiple nuclei. In the oocytes exhibiting PCC, the assembled spindle structure was observed to be an interactive mass, closely associated with condensed chromosomes, but no aster had formed. Regardless of whether they were subjected to IA, IAA, or DA treatments, if the oocytes contained pronuclear-like structures, either one or two asters were observed in proximity to the nuclei. A significantly higher rate of development to blastocysts was achieved in embryos that were immediately activated (IA, 59.1%; IAA, 40.7%) than in those for which activation was delayed (14.2%). The development rate was higher in group IA than in group IAA, but it was not significant (P = 0.089). Following embryo transfer, there was no statistically significant difference in the pregnancy rates (Day 70) between two of the groups (group IA, 11.7%, n = 94 vs. group DA, 12.3%, n = 130; P > 0.05) or live term development (group IA, 4.3% vs. group DA, 4.6%; P > 0.05). Our study has demonstrated that the IA of bovine NT embryos results in embryos with increased competence for preimplantational development. Moreover, PCC was shown to be unnecessary for the reprogramming of a transplanted somatic genome in a cattle oocyte.

Animals↗
PubMed2026

Reprogramming of TLR-Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve Checkpoint Blockade in Prostate Cancer.

UNLABELLED: The limited efficacy of immunotherapies in advanced prostate cancer stems from a tumor microenvironment (TME) in which myeloid-driven immune suppression, stromal remodeling, and metabolic barriers converge to limit antitumor immunity. In this study, we characterized the immunometabolic properties of an ultrasmall prostate-specific membrane antigen-targeting silica particle therapy as a first-in-class strategy to reprogram the Toll-like receptor (TLR)-ferroptosis axis in MYC-driven prostate cancer. As single agents, these particles suppressed lipid and steroid biosynthesis, disrupted lipid peroxidation control, and impaired nutrient flux, sensitizing tumors to ferroptosis. Coordinated redox remodeling, stromal reprogramming, and innate immune activation reversed myeloid suppression and promoted CD8+ T-cell infiltration. When combined with CSF-1R inhibition and immune checkpoint blockade, the particles suppressed tumor growth, extended survival beyond 100 days, and achieved up to 50% complete remission in MYC-overexpressing models. These findings position TLR-ferroptosis axis remodeling as a mechanistic blueprint for rational, particle-driven immunotherapies with broad translational potential in prostate cancer and other immunologically refractory malignancies. SIGNIFICANCE: Clinically validated, PSMA-targeted ultrasmall core-shell silica particles reprogram immunometabolic pathways via a TLR-ferroptosis axis, enabling tumor microenvironment remodeling and potentiating checkpoint blockade in prostate cancer, with translational implications for treatment-resistant disease.

Male↗
PubMed2026

FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury.

Transcriptional reprogramming has an important role in kidney glomerular disease. Using in vivo murine models of podocyte injury, we studied the roles of the FOXC2 and WT1 transcription factors (TFs) in podocyte injury. Podocytes are a crucial cell type of glomeruli, the filtration units of each nephron. Podocyte injury is often the incipient event leading to chronic kidney disease. It is well established that the TFs FOXC2 and WT1 are required in podocytes to maintain the glomerular filtration barrier. Their role in the response to injury is less well understood. Here, we tested the hypothesis that FOXC2 and WT1 act together to mediate transcriptional reprogramming in response to podocyte injury. Similarly to that of WT1, genome-wide FOXC2 binding to target genes is dynamic during the course of injury, initially increasing, but late in injury there is a dramatic decrease in FOXC2 expression and in its binding to target genes. Podocyte-specific inactivation of FoxC2 or Wt1 in adult mice limits the transcriptional response to injury. Correlating FOXC2 and WT1 ChIP-seq analyses demonstrated that they co-bind many genes expressed in podocytes. Thus, reprogramming the transcriptome involves dynamic changes in the binding of FOXC2 and WT1 to their target genes during a reparative injury response.

Animals↗
PubMed2005

Nuclear reprogramming by xenopus oocytes.

The aim of this contribution is to relate amphibian nuclear transplantation work to prospects for stem cell creation and hence to the long-term aim of cell replacement in humans. The methods used include the transplantation of single somatic cell nuclei to enudeated unfertilized eggs of Xenopus, and also the transfer of multiple somatic cell nuclei to the nucleus (germinal vesicle) of a growing ovarian oocyte. A key difference between these types of recipient cell is that eggs immediately induce DNA replication in transplanted nuclei, whereas an oocyte induces no DNA replication, but directly reprograms an injected nucleus to a new pattern of transcriptional activity. We summarize the extent and success of past and current nuclear reprogramming in experiments with enucleated frog eggs, and also those carried out with growing oocytes. We discuss possible mechanisms of nuclear reprogramming, and the possible contribution of such knowledge for stem cell creation and cell replacement in humans.

Animals↗
PubMed2000

Genetic reprogramming of lactate dehydrogenase, citrate synthase, and phosphofructokinase mRNA in bovine nuclear transfer embryos produced using bovine fibroblast cell nuclei.

Adult animal cloning has progressed to allow the production of offspring cloned from adult cells, however many cloned calves die prenatally or shortly after birth. This study examined the expression of three important metabolic enzymes, lactate dehydrogenase (LDH), citrate synthase, and phosphofructokinase (PFK), to determine if their detection in nuclear transfer (NT) embryos mimics that determined for in vitro produced embryos. A day 40 nuclear transfer produced fetus derived from an adult cell line was collected and fetal fibroblast cultures were established and maintained. Reconstructed NT embryos were then produced from this cell line, and RT-PCR was used to evaluate mRNA reprogramming. All three mRNAs encoding these enzymes were detected in the regenerated fetal fibroblast cell line. Detection patterns were first determined for IVF produced embryos (1-cell, 2-cell, 6-8 cell, morula, and blastocyst stages) to compare with their detection in NT embryos. PFK has three subunits: PFK-L, PFK-M, and PFK-P. PFK-L and PFK-P were not detected in bovine oocytes. PFK subunits were not detected in 6-8 cell embryos but were detected in blastocysts. Results from NT embryo RT-PCR demonstrated that PFK was not detected in 8-cell NT embryos but was detected in NT blastocysts indicating that proper nuclear reprogramming had occurred. Citrate synthase was detected in oocytes and throughout development to the blastocyst stage in both bovine IVF and NT embryos. LDH-A and LDH-B were detected in bovine oocytes and in all stages of IVF and NT embryos examined up to the blastocyst stage. A third subunit, LDH-C was not detected at the blastocyst stage in IVF or NT embryos but was detected in all earlier stages and in mature oocytes. In addition, LDH-C mRNA was detected in gonad isolated from the NT and an in vivo produced control fetus. These results indicate that the three metabolic enzymes maintain normal expression patterns and therefore must be properly reprogrammed following nuclear transfer.

Animals↗
PubMed1996

Discordant reprogramming of LPS-stimulated cytokine gene transcription and secretion by macrophages after LPS pretreatment.

Dysregulated macrophage (Mphi) cytokine release occurs during systemic inflammation and may predispose to organ failure. We showed that Mphis pretreated (PreRx) in vitro with low-dose LPSp are "reprogrammed" to release less TNF and more IL-1 in response to subsequent LPS activation (LPSa). The effects of this LPSp "reprogramming" on Mphi cytokine gene transcription were investigated in the present study. Murine peritoneal exudate Mphis were cultured in vitro 48 hr, then PreRx 24 hr +/- 100 ng/ml of LPSp. Cultures were stimulated with 0-1000 ng/ml LPSa and 6-hr supernatant TNF and IL-1 were measured using specific bioassays. Cytokine gene transcription was estimated 6 hr after LPSa using RT-PCR. PreRx with LPSp inhibited TNF and augmented IL-1 release by LPSa. PreRx with LPSp significantly inhibited cytokine gene transcription; however, messages for both TNF and IL-1 were detectable after high-dose LPSa. Despite LPSp inhibition of IL-1 transcription by most LPSa concentrations, IL-1 protein was augmented by PreRx. High-dose LPSa can override LPSp reprogrammed inhibition of cytokine gene transcription, but altered TNF and IL-1 protein release after LPSp may be regulated posttranscriptionally.

Animals↗
PubMed1999

Use of somatic cell fusion to reprogram globin genes.

The developmental phenomenon of hemoglobin switching occurs in all classes of vertebrates and is due to differential regulation of divergent globin genes which are arranged in chromosomally clustered families. By fusing erythroid cells of different developmental programs, it has been shown that erythroid nuclei of either early or late developmental stage can be reprogrammed, i.e. the gene switch can be reversed in adult erythroid nuclei and/or prematurely-induced in fetal/embryonic erythroid nuclei. Experiments with heterokaryons demonstrate that the reprogramming is due to trans-acting factors that are developmental-stage-specific. These results suggest the feasibility of using fusisome-carried sets of nuclear factors to reprogram somatic cells.

Animals↗
PubMed1995

Reprogramming of rye rDNA in triticale during microsporogenesis.

To test the hypothesis that interspecific genomic and chromosome interactions leading to nucleolar dominance could be reprogrammed in meiosis, we compared the expression of distinct nucleolar organizing region (NOR) loci in hexaploid triticale root tip meristematic cells, pollen mother cells and young pollen grains. Interphase and metaphase cells were silver stained to quantify nucleoli and active NOR loci respectively. A marked difference in the ribosomal RNA gene activity of each locus was observed when different types of cells were compared: in somatic and pollen mother cells, rRNA gene activity was mainly restricted to major wheat NORs (1B and 6B) with only a small contribution from rye NORs (1R). In contrast, in young pollen grains, all NORs present, including the 1R NORs, were consistently active. The expression of all NORs just after meiosis is considered to be a consequence of meiotic reprogramming of rye origin rDNA. Gene reprogramming mediated by the resetting of methylation patterns established early in embryogenesis is suggested to be responsible for the differential expression of the NORs of rye origin in distinct developmental stages of triticale.

DNA, Plant↗
PubMed2000

Nuclear transfer, genome reprogramming and novel opportunities in cell therapy.

The knowledge of the molecular mechanism involved in cell differentiation during embryonic development is central for the understanding of differentiative processes including those involved in the progression of genetic diseases. This knowledge would permit the development of new strategies for cell and gene therapies. It has recently been shown that mice can develop to term enucleated oocytes injected with the nuclei of somatic cells. These experiments demonstrate the capacity of the mouse oocyte to remodel the genetic programme of a somatic cells nucleus in order to make it capable of initiating and continuing embryonic development. The activation of zygotic genes occurs in the mouse by the 2-cell stage and it is a crucial event in the life of the newly formed mouse embryo as lack or wrong timing of zygotic gene expression leads to the death of the embryo. For these reasons the gentic modifications (reprogramming) induced by the oocyte over the newly injected somatic nucleus must be completed before zygotic genome activation occurs. The understanding of the mechanisms that intervene in the processes of cell differentiation and in those that make it a reversible process, would allow to repeat the process of nucleus reprogramming in an in vitro system, without the use of the female gamete. Here we will describe some of the genome modifications that might be involved in the reprogramming process following the transfer of a terminally differentiated somatic nucleus into the cytoplasm of an enucleated oocyte.

Animals↗
PubMed2004

Differential DNA methylation reprogramming of various repetitive sequences in mouse preimplantation embryos.

Genome-wide changes of DNA methylation by active and passive demethylation processes are typical features during preimplantation development. Here we provide an insight that epigenetic reprogramming of DNA methylation is regulated in a region-specific manner, not a genome-wide fashion. To address this hypothesis, methylation states of three repetitive genomic regions were monitored at various developmental stages in the mouse embryos. Active demethylation was not observed in the IAP sequences whereas methylation reprogramming of the satellite sequences was regulated only by the active mechanism. Etn elements were actively demethylated after fertilization, passively demethylated by the 8-cell stage, and de novo methylated at the morular and blastocyst stages, showing dynamic epigenetic changes. Thus, our findings suggest that the specific genomic regions or sequences may spatially/temporally have their unique characteristics in the reprogramming of the DNA methylation during preimplantation development.

Animals↗