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Results for “cell fate plasticity”

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At least 55 records · Page 3Linked to original sources

PubMed2004

A new model for olfactory placode development.

The peripheral nervous system of vertebrate animals arises primarily from the interaction of cranial neural crest and sensory placodes. Placodes are described as thickenings of ectoderm that arise through cell division during neural tube formation. The olfactory sensory system is one component of the peripheral nervous system that arises from paired sensory placodes during development. The olfactory placodes give rise to the primary sensory neurons, support cells and basal cells of the olfactory epithelium. Recent evidence from work in zebrafish and chick suggests that the olfactory and auditory placodes arise from large fields of cells that converge to form the sensory placode. The olfactory placodes arise from within the neural plate, and cell division is apparent only after the sensory placodes are morphologically distinct. As the olfactory placode is forming, its precursors must segregate from their neighboring fields which will give rise to the adenohypophyseal placode, cranial neural crest, and telencephalon. Analysis has shown that the endocrine cells thought to arise from the olfactory placode originate in the neighboring adenohypophyseal and cranial neural crest domains. The borders separating the domains are plastic, where cells sort as they move, and cell fate is dependent on the identity of neighbors once the cells have converged to form the sensory placode. Thus there is degeneracy built into the system such that cells accommodate changes in the environment until cell migrations controlling the formation of the sensory placodes are complete.

Animals↗

PubMed2004

Involvement of Notch signaling in hippocampal synaptic plasticity.

During development of the nervous system, the fate of stem cells is regulated by a cell surface receptor called Notch. Notch is also present in the adult mammalian brain; however, because Notch null mice die during embryonic development, it has proven difficult to determine the functions of Notch. Here, we used Notch antisense transgenic mice that develop and reproduce normally, but exhibit reduced levels of Notch, to demonstrate a role for Notch signaling in synaptic plasticity. Mice with reduced Notch levels exhibit impaired long-term potentiation (LTP) at hippocampal CA1 synapses. A Notch ligand enhances LTP in normal mice and corrects the defect in LTP in Notch antisense transgenic mice. Levels of basal and stimulation-induced NF-kappa B activity were significantly decreased in mice with reduced Notch levels. These findings suggest an important role for Notch signaling in a form of synaptic plasticity known to be associated with learning and memory processes.

Animals↗

PubMed2003

Cell differentiation and cell fate during urodele tail and limb regeneration.

One of the most striking natural examples of adult tissue plasticity in vertebrates is limb and tail regeneration in urodele amphibians. In this setting, amputation triggers the destabilization of cell differentiation and the production of progenitor cells that extensively proliferate and pattern themselves to recreate a perfect replica of the missing part. A precise understanding of which cells dedifferentiate and how plastic they become has recently begun to emerge. Furthermore, information on which developmental gene programs are activated upon injury is becoming better understood. These studies indicate that, upon injury, an unusual cohort of genes are co-expressed. The future challenge will be to link the systems for studying dedifferentiation with activation of gene expression to understand on a molecular level how cells are 'pushed backward' to regenerate a complex structure such as a limb or tail.

Animals↗

PubMed2002

Little evidence for developmental plasticity of adult hematopoietic stem cells.

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.

Animals↗

PubMed2004

Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway.

We show that muscle satellite cells, traditionally considered as committed myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a mesenchymal repertoire extending beyond a mere myogenic potential. Mouse satellite cells from freshly isolated single myofibers, cultured individually in serum-rich growth medium, produced myogenic and non-myogenic clones. Only the myogenic clones expressed muscle-specific transcription factors and formed myotubes. Pax7 was initially expressed in all clones, but subsequently was associated only with the myogenic clones. Some cells in the non-myogenic clones expressed alpha-smooth muscle actin and nestin whereas others differentiated into mature adipocytes. This type of cell composition mirrors characteristics of mesenchymal stem cell progeny. Overall, individual myofibers persistently gave rise to both clonal phenotypes, but the ratio of myogenic to non-myogenic clones randomly varied among fibers. This randomness indicates that clonal dichotomy reflects satellite cell suppleness rather than pre-fated cell heterogeneity. We conclude that satellite cells possess mesenchymal plasticity, being able to commit either to myogenesis or to a mesenchymal alternative differentiation (MAD) program.

Actins↗

PubMed2005

Fate and plasticity of the endoderm in the early chick embryo.

In vertebrates, the endoderm is established during gastrulation and gradually becomes regionalized into domains destined for different organs. Here, we present precise fate maps of the gastrulation stage chick endoderm, using a method designed to label cells specifically in the lower layer. We show that the first population of endodermal cells to enter the lower layer contributes only to the midgut and hindgut; the next cells to ingress contribute to the dorsal foregut and followed finally by the presumptive ventral foregut endoderm. Grafting experiments show that some migrating endodermal cells, including the presumptive ventral foregut, ingress from Hensen's node, not directly into the lower layer but rather after migrating some distance within the middle layer. Cell transplantation reveals that cells in the middle layer are already committed to mesoderm or endoderm, whereas cells in the primitive streak are plastic. Based on these results, we present a revised fate map of the locations and movements of prospective definitive endoderm cells during gastrulation.

Animals↗

PubMed2007

Reprogramming of root epidermal cells in response to nutrient deficiency.

Post-embryonic development of the root system is highly plastic to environmental cues, compensating for the sessile lifestyle of plants. The fate of epidermal cells of Arabidopsis roots is particularly responsive to nutritional signals, leading to an increase in the root's surface area in the absence of the essential but immobile minerals iron, phosphate and manganese. The resulting phenotype is characteristic of the respective condition. Growth under nutrient starvation affects the expression of genes involved in cell specification, indicating that environmental signals are perceived at an early stage of cell development. Cell fate decisions are controlled at different levels, probably integrated at the level of chromatin organization.

Arabidopsis↗

PubMed2006

Apoptosis affects integration frequency: adult stem cells injected in blastocysts show high caspase-3 activity.

Chimeric organisms are commonly generated by injecting stem cells into blastocysts. Embryonic stem cells injected into the blastocoel cavity participate in the further development of the embryo. Adult stem cells have also been used in injection experiments to study their potential plasticity. In this study we focused on the early fate of injected human adult hematopoietic stem cells (HSCs). HSCs were followed immunohistochemically 1-19 h after injection into murine blastocysts. We found that they only rarely attached and integrated into the blastocysts. The high rate of loss of injected cells after prolonged in vitro culture of the chimeras can be explained by apoptosis. Our findings are consistent with previous studies reporting a low rate of integration of adult cells injected to produce chimeric embryos, but this is the first demonstration that the low efficiency of adult stem cell injections into blastocysts is influenced by apoptosis.

Adult↗

PubMed2004

Eph/ephrin signaling in morphogenesis, neural development and plasticity.

Ephrins are cell-surface-tethered ligands for Eph receptors, the largest family of receptor tyrosine kinases. During development, the Eph/ephrin cell communication system appears to influence cell behavior such as attraction/repulsion, adhesion/de-adhesion and migration, thereby influencing cell fate, morphogenesis and organogenesis. During adulthood, the Eph/ephrin system continues to play roles in tissue plasticity, for example in shaping dendritic spines during neuronal plasticity. Mechanistically, Eph-ephrin repulsive behavior appears to require ligand-receptor internalization and signaling to Rho GTPases.

Animals↗

PubMed2025

LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer.

Epigenetic regulation profoundly influences the fate of cancer cells and their capacity to switch between lineages by modulating essential gene expression, thereby shaping tumor heterogeneity and therapy response. In castration-resistant prostate cancer (CRPC), the intricacies behind androgen receptor (AR)-independent lineage plasticity remain unclear, leading to a scarcity of effective clinical treatments. Utilizing single-cell RNA sequencing on both human and mouse prostate cancer samples, combined with whole-genome bisulfite sequencing and multiple genetically engineered mouse models, we investigated the molecular mechanism of AR-independent lineage plasticity and uncovered a potential therapeutic strategy. Single-cell transcriptomic profiling of human prostate cancers, both pre- and post-androgen deprivation therapy, revealed an association between liver kinase B1 (LKB1) pathway inactivation and AR independence. LKB1 inactivation led to AR-independent lineage plasticity and global DNA hypomethylation during prostate cancer progression. Importantly, the pharmacological inhibition of TET enzymes and supplementation with S-adenosyl methionine were found to effectively suppress AR-independent prostate cancer growth. These insights shed light on the mechanism driving AR-independent lineage plasticity and propose a potential therapeutic strategy by targeting DNA hypomethylation in AR-independent CRPC.

Male↗

PubMed2004

Transplantation for stroke.

Stroke is the most common cause of disability in the United States, and one of the leading causes of mortality and disability in the world. The hope that damage to the CNS can be reversed or at least ameliorated is the central idea behind the research into neural repair. The ultimate repair for the brain should restore the entire lost structure and it's function. However, partial benefit is possible from addressing some of the needs of the injured brain. These partial solutions are the basis of current research into brain repair after stroke. An opportunity arises for two kinds of intervention: (1) replacement of neurons; (2) support of existing neurons, to prevent excessive degeneration and promote rewiring and plasticity. Transplantation for stroke in the rat model was regularly reported starting in 1992, demonstrating graft survival and even evidence of connection with the host brain. These studies determined several parameters for future work in stroke models, but ultimately had limited efficacy and did not progress to clinical experiments. A variety of cell types have been tried for restoration of brain function after stroke, mostly in rodent models. Human fetal cells had shown some promise in clinical studies for the treatment of Parkinson's disease. The technical and ethical difficulties associated with these cells promoted a search for alternatives. These include porcine fetal cells, human cultured stem cells, immortalized cell lines, marrow stromal cells, Sertoli cells pineal cells, and other sources. Human clonal cell lines have few ethical limitations, but some questions remain regarding their safety and efficacy. Autologous somatic stem cells are a very attractive source--there are no ethical concerns and graft rejection is not an issue. However, it is not clear that somatic cells can are plastic enough and can be safely induced to a neural fate. Restorative treatment for stroke is a new field of study. Naturally, new ideas abound and many strategies have been suggested and tried. Methods and controversies abound, and include: local delivery of cells to the area of the stroke versus grafting to an area of the brain far removed form the stroke; cell therapy for reconstitution of structure and function versus use of cell grafts to support intrinsic repair and recovery mechanisms; intravascular administration of bone marrow or other stem cells; and combination grafts, or co-grafting of several cell types or cells and other substances. The various strategies address the issue of restorative treatments form different perspectives. Some interventions occur early after stroke, or are intended to preserve existing neural structures. For example, treatment strategies that aim to provide trophic support may demonstrate early beneficial results. Other strategies aim for growth and integration of new neurons to replace those lost after stroke. In this case, early beneficial results are not likely. Functional integration of grafted neurons, if it can ever happen, is likely to require training and exercise of the appropriate capacities. Further advances in preclinical studies of neural transplantation will require improved animal models with increased sensitivity to subtle behavioral and imaging changes. Non-human primate models have been established and may increase in importance as a phase before clinical trials. The future of brain repair for stroke is likely to require some form of combination therapy designed to replace the lost cells and supporting structure, attract new blood supply, support and enhance intrinsic repair and plasticity mechanisms.

Animals↗

PubMed2006

CAR-1 and trailer hitch: driving mRNP granule function at the ER?

The targeting of messenger RNAs (mRNAs) to specific subcellular sites for local translation plays an important role in diverse cellular and developmental processes in eukaryotes, including axis formation, cell fate determination, spindle pole regulation, cell motility, and neuronal synaptic plasticity. Recently, a new conserved class of Lsm proteins, the Scd6 family, has been implicated in controlling mRNA function. Depletion or mutation of members of the Scd6 family, Caenorhabditis elegans CAR-1 and Drosophila melanogaster trailer hitch, lead to a variety of developmental phenotypes, which in some cases can be linked to alterations in the endoplasmic reticulum (ER). Scd6/Lsm proteins are RNA binding proteins and are found in RNP complexes associated with translational control of mRNAs, and these complexes can colocalize with the ER. These findings raise the possibility that localization and translational regulation of mRNAs at the ER plays a role in controlling the organization of this organelle.

Caenorhabditis elegans Proteins↗

PubMed2004

[Mesenchymal stem cells. Differentiation and alternative source of neural tissue].

Embryonic stem cells are a population of cells located in the blastocyst, committed to specific differentiation according to spatial and temporal factors such as age and place of final location. Despite the final fate of hematic cells, hemopoietic cells retain a relative degree of plasticity dependent on environmental factors. Mesenchymal cells are a well differentiated population of bone marrow derived non hemopoietic cells with totipotential properties. The medical interest of such totipotentiality rests in the potential of such cells to repair damaged tissues. Particularly neuronal differentiation from progenitors obtained from mesenchymae non hemopoietic cells offers a new possibility in the field of neural transplantation and tissue engineering to repair functional entities in the nervous system.

Bone Marrow Transplantation↗

PubMed1990

Regenerated hair cells can originate from supporting cell progeny: evidence from phototoxicity and laser ablation experiments in the lateral line system.

The mechanisms that lead to the production of sensory hair cells during regeneration have been investigated by using 2 different procedures to ablate preexisting hair cells in individual neuromast sensory epithelia of the lateral line in the tails of salamanders, then monitoring the responses of surviving cells. In one series of experiments, fluorescent excitation was used to cause the phototoxic death of hair cells that selectively take up the pyridinium dye DASPEI. In the other experiments, the ultraviolet output of a pulsed neodymium-YAG laser was focused to a microbeam through a quartz objective lens in epi-illumination mode and used to selectively kill individual unlabeled hair cells while the cells were simultaneously imaged by transmitted light DIC microscopy. Through observation of the treated neuromasts in vivo, these experiments demonstrated that mature sensory epithelia that have been completely depleted of hair cells can still generate new hair cells. Preexisting hair cells are not necessary for regeneration. Immediately after the ablations the only resident cells in the sensory epithelia were supporting cells. These cells were observed to divide at rates that were increased over control values, and eventually those cell divisions gave rise to progeny that differentiated as hair cells, replacing those that had been killed. Macrophages were active in these epithelia, and their phagocytic activity had a significant influence on the standing population of cells. The first new hair cells appeared 3-5 d after the treatments, and additional hair cells usually appeared every 1-2 d for at least 2 weeks. We conclude that the fate of the progeny produced by supporting cell divisions is plastic to a degree, in that these progeny can differentiate either as supporting cells or as hair cells in epithelia where hair cells are missing or depleted.

Ambystoma↗

PubMed1993

[Recent advances in the molecular biology of voltage-sensitive Na+ channels].

Na+ channels play a crucial role in generating action potentials in neurones and other excitable cells. alpha-subunits, composed of four homologous repeats, are responsible for most of the Na+ channel properties. The combination of molecular biology with electro-physiological tools has proved useful for understanding the molecular mechanism of the channel function. Activation, inactivation and ion permeation occur, based on Segment 4, III-IV linker, the region intervened by Segment 5 and 6, respectively. Mutations in a human skeletal muscle Na+ channel gene cause heritable muscle disorders, hyperkalemic periodic paralysis and paramyotonica congenita. Future directions in Na+ channel studies may include gene regulation of the Na+ channel related to neural cell fate and subcellular localization of channel molecules concurrent with plasticity or development.

Action Potentials↗

PubMed1997

Early- and late-migrating cranial neural crest cell populations have equivalent developmental potential in vivo.

We present the first in vivo study of the long-term fate and potential of early-migrating and late-migrating mesencephalic neural crest cell populations, by performing isochronic and heterochronic quail-to-chick grafts. Both early- and late-migrating populations form melanocytes, neurons, glia, cartilage and bone in isochronic, isotopic chimeras, showing that neither population is lineage-restricted. The early-migrating population distributes both dorsally and ventrally during normal development, while the late-migrating population is confined dorsally and forms much less cartilage and bone. When the late-migrating population is substituted heterochronically for the early-migrating population, it contributes extensively to ventral derivatives such as jaw cartilage and bone. Conversely, when the early-migrating population is substituted heterochronically for the late-migrating population, it no longer contributes to the jaw skeleton and only forms dorsal derivatives. When the late-migrating population is grafted into a late-stage host whose neural crest had previously been ablated, it migrates ventrally into the jaws. Thus, the dorsal fate restriction of the late-migrating mesencephalic neural crest cell population in normal development is due to the presence of earlier-migrating neural crest cells, rather than to any change in the environment or to any intrinsic difference in migratory ability or potential between early- and late-migrating cell populations. These results highlight the plasticity of the neural crest and show that its fate is determined primarily by the environment.

Animals↗

PubMed1998

Plasticity and stem cells in the vertebrate nervous system.

How and when do vertebrate neural precursor cells choose their fates? While some studies suggest a series of commitments on the road to fate choice, many recent experiments indicate that precursor fate choices can often be changed. Additionally, the identification of common gene control mechanisms in precursors suggest that these cells share fundamental properties throughout development.

Animals↗

PubMed2005

Transcriptional regulation in myelopoiesis: Hematopoietic fate choice, myeloid differentiation, and leukemogenesis.

Myeloid cells (granulocytes and monocytes) are derived from multipotent hematopoietic stem cells. Gene transcription plays a critical role in hematopoietic differentiation. However, there is no single transcription factor that is expressed exclusively by myeloid cells and that, alone, acts as a "master" regulator of myeloid fate choice. Rather, myeloid gene expression is controlled by the combinatorial effects of several key transcription factors. Hematopoiesis has traditionally been viewed as linear and hierarchical, but there is increasing evidence of plasticity during blood cell development. Transcription factors strongly influence cellular lineage during hematopoiesis and expression of some transcription factors can alter the fate of developing hematopoietic progenitor cells. PU.1 and CCAAT/enhancer-binding protein alpha (C/EBPalpha) regulate expression of numerous myeloid genes, and gene disruption studies have shown that they play essential, nonredundant roles in myeloid cell development. They function in cooperation with other transcription factors, co-activators, and co-repressors to regulate genes in the context of chromatin. Because of their essential roles in regulating myeloid genes and in myeloid cell development, it has been hypothesized that abnormal expression of PU.1 and C/EBPalpha would contribute to aberrant myeloid differentiation, i.e. acute leukemia. Such a direct link has been elusive until recently. However, there is now persuasive evidence that mutations in both PU.1 and C/EBPalpha contribute directly to development of acute myelogenous leukemia. Thus, normal myeloid development and acute leukemia are now understood to represent opposite sides of the same hematopoietic coin.

Animals↗