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 235 records · Page 13Linked to original sources
PubMed2007

Donor cell differentiation, reprogramming, and cloning efficiency: elusive or illusive correlation?

Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages.

Animals↗
PubMed1999

Genetic reprogramming following nuclear transplantation in Amphibia.

Specialized cells are generally unable to switch from one type to another. For example, muscle cells can not be converted to intestine, brain, skin, etc. However, the nucleus of a specialized cell, such as muscle, can be transplanted to an enucleated egg, and the resulting combination will form all these and most other cell types. Likewise somatic cell nuclei injected into oocytes will switch their pattern of gene expression to conform to that of an oocyte, repressing some genes and activating others. This article reviews what is known of the mechanisms involved in these examples of nuclear reprogramming.

Amphibians↗
PubMed1999

Reprogramming a somatic nucleus by trans-modification activity in germ cells.

The germ cell lineage is totipotent insofar as it provides a link between an individual and the subsequent generations. There is a series of characteristic genomic modifications in germ cells that distinguish this lineage from somatic cells. These modifications include extensive demethylation of the genome, erasure of allele-specific methylation of imprinted loci and re-activation of the silent X chromosome. To test if this is an active process capable of reprogramming a somatic nucleus, we prepared germ cell-somatic cell hybrids. A dominant trans modification activity was detected in germ cells that was capable of inducing similar modifications in the somatic nucleus. This experimental system can therefore be used to study how determined cell state can be reversed by specific genomic modifications.

Animals↗
PubMed2006

Toward reprogramming cells to pluripotency.

The possibility of turning one somatic cell type into another may in the long run have beneficial applications in regenerative medicine. Somatic cell nuclear transfer (therapeutic cloning) may offer this possibility; however, ethical guidelines prevent application of this technology in many in countries. As a result, alternative approaches are being developed for altering cell fate. This communication discusses recent non-nuclear transfer-based in vitro approaches for reprogramming cells and enhancing their potential for differentiation toward various lineages.

Animals↗
PubMed2003

[Receptors and signal proteins of the innate immune system as new targets in sepsis therapy. Reprogramming of the immune response].

During polymicrobial sepsis,microbial pathogens and their products activate the innate immune system through signaling receptors of the Toll-like receptor (TLR) family, resulting in hyperinflammation and organ injury. The analysis of preclinical mouse models has shown that inactivation of the common TLR signaling adaptor protein MyD88 prevents the hyperinflammatory response and improves survival.Importantly, MyD88 deficiency does not impair antibacterial defense mechanisms.Thus,TLRs and proteins involved in TLR signaling may represent interesting targets for the development of new drugs for reprogramming pathophysiological immune responses during sepsis.

Animals↗
PubMed1991

Reprogramming of myosin light chain 1/3 expression in muscle heterokaryons.

Fast myosin light chain (MLC) 1/3 is one of the few genes which regulates transcript production at both transcriptional and post-transcriptional levels, utilizing two functionally distinct promoters coupled with alternatively spliced exons. The transcriptional process controlling expression from this single gene locus is developmentally regulated, such that MLC 1 precedes MLC 3 during myogenesis. Results from our RNA analyses demonstrate that in differentiated rat L6E9 muscle, MLC 3 is the sole isoform expressed from the MLC 1/3 locus. However, we also show that by generating rat L6E9:mouse C2 muscle heterokaryons, MLC 1 expression from the L6E9 MLC locus can be induced. In addition to novel rat MLC 1 expression in the C2:L6E9 heterokaryons, we show that the synthesis profile of rat MLC 3 mRNA is also altered relative to L6E9 muscle cultured alone. Additional experiments demonstrate that the reprogramming of rat MLC 1 and 3 expression in the muscle heterokaryons requires that C2 and L6E9 nuclei be contained within a common cytoplasm. These results demonstrate that expression from the MLC 1/3 gene is "plastic," and is not under the control of a strict developmental program but, rather, can be modified by the environmental milieu.

Animals↗
PubMed1975

Reprogramming in the absence of DNA synthesis in Galleria larval epidermis.

Larval epidermal cells from a day-1 penultimate instar Galleria larva on implantation into day-5 last instar larva metamorphose and deposit a pupal cuticle at the same time as the host pupates. DNA synthesis in the implanted larval cell was monitored with 3-H-thymidine. Various regimens of 3-H-thymidine application were used and under no conditions did the larval cells incorporate label during the period from implantation to deposition of pupal cuticle. This suggests that a wax moth larval ectoderm cell can reprogram its genome to secrete a pupal cuticle without a precedent cell division.

Animals↗
PubMed1984

Gene expression of differentiated parent in teratocarcinoma cell hybrids. Repression or reprogramming?

The hybrid cell line H422 was constructed by fusing embryonal carcinoma (EC) cells of the PCC4AzaRCapR cell line with lymphocytes from a 129-tw32 mouse inbred strain female. An apparently complete extinction of stage-specific gene products of the lymphocyte parent was inferred from comparison of protein maps in two-dimensional PAGE of parental and hybrid cells, and from the reactivity patterns of monoclonal antibodies in radioimmunobinding assays. Furthermore, the hybrid cells display a true EC phenotype and EC functions, tumorigenicity and pluripotency. Taken together, the available evidence suggests either that the lymphocyte genome is a 'silent passenger' as far as the differentiated functions of hybrid cells are concerned, or that the developmentally restricted lymphocyte genome is reprogrammed in the hybrid cells back to a non-determined stage and both genomes thus act in a concerted manner.

Animals↗
PubMed1984

Reprogramming cell differentiation in the absence of DNA synthesis.

We examined whether the activation of muscle gene expression in nonmuscle cells required DNA synthesis. Human fibroblasts from amniotic fluid and fetal lung were fused with differentiated mouse muscle cells in the presence or absence of the DNA synthesis inhibitor, cytosine arabinoside. In the stable heterokaryons formed, the human contractile enzyme, MM-creatine kinase (CK), and the cell surface antigen, 5.1H11, were detected in comparable amounts regardless of whether DNA synthesis had occurred. A single cell analysis revealed that the efficiency of gene activation was high and that DNA synthetic activity was not affected by the ratio of muscle to nonmuscle nuclei in the heterokaryons. In addition, muscle gene expression was not restricted to the G1 phase of the cell cycle. We conclude that cell differentiation can be reprogrammed in heterokaryons regardless of cell cycle phase and in the absence of detectable DNA synthesis.

Animals↗
PubMed1986

Rapid reprogramming of globin gene expression in transient heterokaryons.

Interspecific heterokaryons were formed by fusing adult mouse erythroleukemia (MEL) cells and human embryonic/fetal erythroid (K562) cells with each other, or with a variety of mouse and human nonerythroid cell types. Analysis of total cellular RNA isolated 24 hr after fusion revealed that normally inactive globin genes can be activated in these "transient" heterokaryons, in which the nuclei do not fuse. In general, the types of globin genes expressed in the donor erythroid cell are activated in the nucleus of the recipient cell. Therefore, erythroid cells contain transacting regulatory factors that are capable of activating the expression of globin genes in a stage- and tissue-specific manner. These observations also indicate that globin genes are not irreversibly repressed in differentiated cells and that their expression can be rapidly reprogrammed in the presence of the appropriate regulatory factors.

Animals↗
PubMed2006

Dendritic cells post-maturation are reprogrammed with heightened IFN-gamma and IL-10.

Mature dendritic cells (mDCs) undergo "exhaustion" in producing cytokines. Nevertheless, whether this "exhaustion" of mDCs is selective to certain cytokines, or whether mDCs have specific cytokine-producing profiles has yet to be defined. Herein, we investigated the cytokine production in vitro by immature DCs (iDCs) and LPS-induced mDCs. Compared to iDCs, mDCs produced comparable levels of IL-6 and TNF-alpha. Strikingly, mDCs produced significantly higher IFN-gamma and IL-10. IL-12 production of mDCs was suppressed. Kinetic studies of the responses of iDCs and mDCs to LPS or CD40L showed that mDCs acquired progressively heightened activity in producing IFN-gamma and IL-10. TNF-alpha-, IL-6-producing capability of mDCs was maintained. Nevertheless, IL-12 production by mDCs was not recovered at any time point. Mature DCs were potent in priming both Th1 and Th2 cells. In conclusion, upon maturation, DCs are reprogrammed with a distinct cytokine-secreting profile, which may play an important role in regulating T cell functions.

Animals↗
PubMed2006

Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation.

It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/mul). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations.

Animals↗
PubMed2004

Reprogramming committed B lineage cells.

It is generally assumed that once a cell commits to a certain lineage it no longer can change its fate. A new study in this issue of Cell provides compelling evidence that committed mature B lineage cells can be reprogrammed to become macrophages.

Animals↗
PubMed2005

ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle.

The transition from juvenile to adult life is accompanied by programmed remodeling in many tissues and organs, which is key for organisms to adapt to the demand of the environment. Here we report a novel regulated alternative splicing program that is crucial for postnatnal heart remodeling in the mouse. We identify the essential splicing factor ASF/SF2 as a key component of the program, regulating a restricted set of tissue-specific alternative splicing events during heart remodeling. Cardiomyocytes deficient in ASF/SF2 display an unexpected hypercontraction phenotype due to a defect in postnatal splicing switch of the Ca(2+)/calmodulin-dependent kinase IIdelta (CaMKIIdelta) transcript. This failure results in mistargeting of the kinase to sarcolemmal membranes, causing severe excitation-contraction coupling defects. Our results validate ASF/SF2 as a fundamental splicing regulator in the reprogramming pathway and reveal the central contribution of ASF/SF2-regulated CaMKIIdelta alternative splicing to functional remodeling in developing heart.

Alternative Splicing↗
PubMed2005

Nuclear reprogramming by human embryonic stem cells.

Embryonic stem cells have two unique properties. They are capable of indefinite self-renewal and, being pluripotent, they can differentiate into all possible cell types, including germ cells. A new study by Cowan et al. (2005) published in Science shows that human embryonic stem cells are able to reprogram the nuclei of fully differentiated human somatic cells, apparently conferring on them a pluripotent state.

Cell Nucleus↗
PubMed2006

A transcriptional logic for nuclear reprogramming.

Limitations on a differentiated cell's pluripotency can be erased by nuclear transfer or by fusion with embryonic stem cells, but attempts to recapitulate this process of nuclear reprogramming by molecular means have failed. In this issue of Cell, Takahashi and Yamanaka (2006) take a rational approach to identifying a suite of embryonic transcription factors whose overexpression restores pluripotency to adult somatic cells.

Animals↗
PubMed2026

Localized PD-1 CAR T therapy reprograms neuroinflammation.

B cell-depleting therapies are effective in multiple sclerosis (MS), yet some patients relapse, underscoring the need for more precise interventions. To identify new therapeutic targets, we generated a single-cell RNA sequencing (scRNA-seq) atlas of cerebrospinal fluid (CSF), brain, and blood from non-inflammatory controls and patients with MS or other neuroinflammatory diseases. We found disease-associated enrichment of class-switched immunoglobulin G+ (IgG+) B cells and plasma cells in MS CSF. Unbiased analysis identified a rare disease-enriched subset of activated, T cell receptor (TCR)-restricted, PD-1+ T follicular helper-like cells with B cell-recruiting features. To target this population, we developed PD-1-directed chimeric antigen receptor (CAR) T cells that selectively depleted pathogenic PD-1+ CD4 T cells and locally released IL-10. This strategy attenuated central nervous system (CNS) inflammation, reprogrammed the local immune milieu, and improved clinical outcomes across murine neuroinflammation models. These findings define a CNS-localized adaptive immune circuit in MS and nominate programmable PD-1 CAR T cells as a strategy to disrupt it.

Animals↗
PubMed2026

Translational reprogramming of TGF-β signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGFβR1. This amplifies downstream TGF-β/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGFβR1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male↗