Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Multipotent Stem Cells”

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 1,711 records · Page 95Linked to original sources
PubMed2004

Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.

How does an emerging transcriptional programme regulate individual genes as stem cells undergo lineage commitment, differentiation and maturation? To answer this, we have analysed the dynamic protein/DNA interactions across 130 kb of chromatin containing the mouse alpha-globin cluster in cells representing all stages of differentiation from stem cells to mature erythroblasts. The alpha-gene cluster appears to be inert in pluripotent cells, but priming of expression begins in multipotent haemopoietic progenitors via GATA-2. In committed erythroid progenitors, GATA-2 is replaced by GATA-1 and binding is extended to additional sites including the alpha-globin promoters. Both GATA-1 and GATA-2 nucleate the binding of various protein complexes including SCL/LMO2/E2A/Ldb-1 and NF-E2. Changes in protein/DNA binding are accompanied by sequential alterations in long-range histone acetylation and methylation. The recruitment of polymerase II, which ultimately leads to a rapid increase in alpha-globin transcription, occurs late in maturation. These studies provide detailed evidence for the more general hypothesis that commitment and differentiation are primarily driven by the sequential appearance of key transcriptional factors, which bind chromatin at specific, high-affinity sites.

Acetylation↗
PubMed2003

Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia.

After late embryogenesis, new neurons are continuously added to the olfactory bulb (OB) from stem cells located in the forebrain subventricular zone. Nonetheless, stem cells have not been described within the embryonic olfactory bulb. Here we report the isolation of local olfactory bulb stem cells from the embryonic day 12.5-14.5 mouse embryo. These cells were 99.2% nestin positive and proliferated extensively in culture to at least 150 cell doublings. Clonal analysis demonstrated that neurons (TuJ1(+)), astrocytes (GFAP(+)), and oligodendrocytes (O4(+)) could be generated from single-plated cells, indicating that they are multipotent. At least 90% of proliferating cells expressed insulin-like growth factor-I (IGF-I), (pro)insulin, and their cognate receptors; these growth factors collaborated with fibroblast growth factor-2 plus epidermal growth factor (EGF) to promote stem cell proliferation and sphere formation. Cells from Igf-I(-)/- mice, however, proliferated as extensively as did Igf-I(+/+) cells. Differentiation and survival of stem cell-generated neurons and glia showed strong dependence on exogenous IGF-I, but oligodendrocyte differentiation also required insulin at low concentration. Furthermore, the percentages of stem cell-generated neurons, astrocytes, and oligodendrocytes were markedly lower in the cultures prepared from the Igf-I(-)/- mice compared with those of Igf-I(+/+). Concordantly, lack of IGF-I resulted in abnormal formation of the olfactory bulb mitral cell layer and altered radial glia morphology. These results support the presence within the embryonic mouse olfactory bulb of stem cells with specific requirements for insulin-related growth factors for proliferation or differentiation. They demonstrate that IGF-I is an endogenous factor regulating the differentiation of stem and other precursor cells within the olfactory bulb.

Animals↗
PubMed2004

Differential regulation of the mitochondrial and death receptor pathways in neural stem cells.

Despite an increasing interest in neural stem cell (NSC) research, relatively little is known about the biochemical regulation of cell death pathways in these cells. We demonstrate here, using murine-derived multipotent C17.2 NSCs, that cells undergo mitochondria-mediated cell death in response to apoptotic stimuli such as oxidative stress induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). In particular, treated cells exhibited apoptotic features, including Bax translocation, cytochrome c release, activation of caspase-9 and -3, chromatin condensation and DNA fragmentation. Although C17.2 cells possess the Fas receptor and express procaspase-8, agonistic Fas mAb treatment failed to induce apoptosis. Fas treatment activated the extracellular signal-regulated protein kinase (ERK) pathway, which may have an antiapoptotic as well as a growth stimulating role. Combined, our findings indicate that while NSCs are sensitive to cytotoxic stimuli that involve an engagement of mitochondria, Fas treatment does not induce death and may have an alternative role.

Amino Acid Chloromethyl Ketones↗
PubMed2004

Telomerase deficiency impairs differentiation of mesenchymal stem cells.

Expression of telomerase activity presumably is involved in maintaining self-replication and the undifferentiated state of stem cells. Adult mouse bone marrow mesenchymal stem cells (mMSCs) are multipotential cells capable of differentiating into a variety of lineage cell types, including adipocytes and chondrocytes. Here we show that the lacking telomerase of mMSC lose multipotency and the capacity to differentiate. Primary cultures of mMSCs were obtained from both telomerase knockout (mTR(-/-)) and wild-type (WT) mice. The MSCs isolated from mTR(-/-) mice failed to differentiate into adipocytes and chondrocytes, even at early passages, whereas WT MSCs were capable of differentiation. Consistent with other cell types, late passages mTR(-/-)MSCs underwent senescence and were accompanied by telomere loss and chromosomal end-to-end fusions. These results suggest that in addition to its known role in cell replication, telomerase is required for differentiation of mMSCs in vitro. This work may be significant for further potentiating adult stem cells for use in tissue engineering and gene therapy and for understanding the significance of telomerase expression in the process of cell differentiation.

Adipocytes↗
PubMed2004

Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells.

Single-cell transplantation analysis revealed that the cells that had the strongest dye efflux activity ("Tip"-SP cells) and had the phenotype CD34- c-Kit+ Sca-1+ Lin- (CD34- KSL cells) exhibited very strong proliferation and multilineage differentiation capacity. Ninety-six percent of the lethally irradiated mice that received a single "Tip"-SP CD34- KSL cell showed significant donor cell engraftment for long term. These findings support the hypothesis that "Tip"-SP CD34- KSL cells represent the most primitive hematopoietic stem cells that are capable of migrating into the primary site and surviving and/or proliferating with nearly absolute efficiency. This led us to propose high marrow-seeding efficiency as a specific characteristic of primitive HSCs, in addition to their self-renewal and multipotent capacity.

Animals↗
PubMed2006

Demonstration of hematopoietic stem cells in ginbuna carp (Carassius auratus langsdorfii) kidney.

A model system of ginbuna carp (clonal triploid fish, Carassius auratus langsdorfii) and ginbuna-goldfish hybrids (tetraploid fish, having three sets of chromosomes from a triploid clone and a haploid set of chromosomes from goldfish) was employed to demonstrate the presence of hematopoietic stem cells (HSCs) in kidney hematopoietic tissues. Kidney hematopoietic cells were obtained from ginbuna carp (S3n, donor) and injected into a ginbuna-gold fish hybrid (S4n, recipient) via the caudal sinus. The percentage of S3n cells in the S4n blood was measured by flow cytometry by the difference of DNA content from 3 to 18 months after the injection. Donor-derived major types of blood cells including erythrocytes, thrombocytes, neutrophils, basophils, monocytes, T and B lymphocytes were detected in the recipient blood over a long period (9-18 month posttransplantation). Moreover, recipient lympho-hematopoietic organs such as head kidney, body kidney, spleen, and thymus were reconstituted by donor cells. These results indicate that long-term multipotent repopulating HSCs reside in the donor kidney.

Acridine Orange↗
PubMed2003

Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells: an in vitro model to study islet differentiation.

Embryonic stem (ES) cells differentiating in vitro reproduce many facets of early embryonic development, including the expression of developmentally regulated transcription factors and the differentiation of multipotent precursor cells. ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal homeobox 1 (PDX1)-positive pancreatic precursor cells, early endocrine cell progenitors, and islet hormone-producing cells. Following growth and differentiation in nonselective medium containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones: insulin, glucagon, somatostatin, and pancreatic polypeptide. PDX1 immunostaining cells appeared first, before hormone-positive cells had emerged. Hormone-positive cells appeared within focal clusters of cells coexpressing PDX1 and the nonclassical hormone markers peptide YY (YY) and islet amyloid polypeptide (IAPP) in combination with the definitive hormones, characteristic of endocrine cells appearing during early pancreaticogenesis. This system allows the investigation of many facets of islet development since it promotes the appearance of the complete range of islet phenotypes and reproduces important developmental stages of normal islet cytodifferentiation in differentiating ES cell cultures.

Amyloid↗
PubMed2005

Long-term proliferation of human embryonic stem cell-derived neuroepithelial cells using defined adherent culture conditions.

Research on the cell fate determination of embryonic stem cells is of enormous interest given the therapeutic potential in regenerative cell therapy. Human embryonic stem cells (hESCs) have the ability to renew themselves and differentiate into all three germ layers. The main focus of this study was to examine factors affecting derivation and further proliferation of multipotent neuroepithelial (NEP) cells from hESCs. hESCs cultured in serum-deprived defined medium developed distinct tube structures and could be isolated either by dissociation or adherently. Dissociated cells survived to form colonies of cells characterized as NEP when conditioned medium from human hepatocellular carcinoma HepG2 cell line (MEDII) was added. However, cells isolated adherently developed an enriched population of NEP cells independent of MEDII medium. Further characterization suggested that they were NEP cells because they had a similar phenotype profile to in vivo NEP cells and expression SOX1, SOX2, and SOX3 genes. They were positive for Nestin, a neural intermediate filament protein, and Musashi-1, a neural RNA-binding protein, but few cells expressed further differentiation markers, such as PSNCAM, A2B5, MAPII, GFAP, or O4, or other lineage markers, such as muscle actin, alpha fetoprotein, or the pluripotent marker Oct4. Further differentiation of these putative NEP cells gave rise to a mixed population of progenitors that included A2B5-positive and PSNCAM-positive cells and postmitotic neurons and astrocytes. To proliferate and culture these derived NEP cells, ideal conditions were obtained using neurobasal medium supplemented with B27 and basic fibroblast growth factor in 5% oxygen. NEP cells were continuously propagated for longer than 6 months without losing their multipotent cell characteristics and maintained a stable chromosome number.

Animals↗
PubMed1997

A comparative analysis of the transplant potential of umbilical cord blood versus mobilized peripheral blood stem cells.

Human umbilical cord blood (UCB) is currently considered as a third source of hematopoietic stem cells for transplantation, following the bone marrow and growth-factor-mobilized peripheral blood (MPB). To evaluate the potential benefits of UCB, we performed a comparative study of the properties of the stem cells in UCB and MPB samples. CD 34+ cell determination and CFU-GM colony assay showed a lower frequency of committed progenitors in UCB than in MPB. In contrast, a higher of the CD 34+ CD 38- subset in UCB suggested that more primitive, multipotent progenitors are enriched in UCB than in MPB. Phenotypic analysis of UCB lymphocytes revealed a reduced level of T cell subsets, especially cytotoxic CD 8+ lymphocytes, which might minimize graft versus host disease in clinical practice. In conclusion, UCB is an attractive alternative source for stem cell transplantation, but ex vivo expansion of stem/progenitor cells could be effective for attaining rapid and safer hemopoietic reconstruction.

Blood Cell Count↗
PubMed1993

The ontogeny of the neural crest.

The neural crest is part of a larger embryonic structure, the neural folds, belonging to the neural primordium of the Vertebrate embryo. The neural fold is formed by the anterior and lateral ridges of the neural anlage, which fuse mediodorsally when the neural tube closes. Anteriorly, the epithelium of the neural fold does not convert into mesenchymal cells and yields Rathke's pouch, the olfactory organ and the epithelium of the mouth roof, of the upper lip and of the frontal region of the head. From the level of the diencephalon (at the level of the epiphysis) downwards the neural fold epithelium undergoes the epitheliomesenchymal transition and yields the neural crest cells which become later on highly diversified and form various structures and tissues throughout the body. A large amount of data have shown that the environmental cues exerted on crest cells both during their migration and when they have reached their target sites are critical in determining their fate. In order to understand the mechanisms through which environmental factors influence crest cell differentiation, the developmental capacities of single neural crest cells were investigated at different time points of their ontogeny. Single cell cultures of crest cells have revealed that already at the migratory stage the neural crest is made up of cells at different states of determination. In particular, the analysis of clones obtained from single cell cultures of cephalic migratory crest cells has shown that, although many clonogenic cells are multipotent to varying degrees, others are committed to give rise to one single derivative. Totipotent progenitors able to generate representatives of virtually all the phenotypes (neuronal, glial, melanocytic and mesectodermal) encountered in cephalic neural crest derivatives were also found. We proposed that they represent stem cells analogous to those which in the hemopoietic system generate the various types of blood cells. The neural crest stem cell gives rise to diverse progenitors that become progressively restricted in their potentialities according to an essentially stochastic mechanism while dividing during and after completion of the migration process. Similar cloning experiments of crest cells that have already reached their target organs, i. e. sensory ganglia or enteric plexuses, showed that the phenotypic repertoire expressed by crest-derived cells decreases with increasing embryonic age. Efforts are made to elucidate the nature of the factors which influence either the survival and/or the differentiation of neural crest cells in the various types of environments in which they evolve.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors.

Mice that lack the transcription factors encoded by the E2A gene or the receptor for interleukin 7 (IL-7R) have severe overlapping defects in lymphocyte development. Here, we show that E2A proteins are required for the survival of early T-lineage cells; however, they function through a pathway that is distinct from the survival pathway initiated by IL-7R signaling. While E2A proteins are required to suppress caspase 3 activation, ectopic expression of the anti-apoptotic protein Bcl-2 is not sufficient to overcome the lymphopoietic defects observed in the absence of E2A. Remarkably, mice that lack both IL-7Ralpha and E47 display a synergistic decrease in the number of T-cell, NK-cell and multipotent progenitors in the thymus, indicating that these distinct survival pathways converge to promote the development of multipotent lymphoid progenitors.

Animals↗
PubMed2006

Molecular switches and developmental potential of adult stem cells.

Stem cell commitment and differentiation entails the successive loss of self-renewal and developmental potential, and results in the final restriction to a terminally differentiated mature cell type. Hematopoiesis, the development of blood cells from hematopoietic stem cells in bone marrow, is particularly well studied, and at different branching points within the hematopoietic system multiple developmental intermediates have been identified. Here we describe a Flt3+ CD11b+ multipotent progenitor that can be amplified in vitro by a specific cytokine combination to high cell numbers, and following adoptive transfer into syngeneic mice, it generates dendritic cells but also additional mature cell types. By employing gene expression profiling with DNA microarrays and knockout mouse models, we demonstrate that the helix-loop-helix (HLH) transcription factor Id2 (inhibitor of DNA binding/differentiation 2) acts as a molecular switch in development of Langerhans cells (LCs), the cutaneous contingent of dendritic cells (DCs), and of specific DC subsets and B cells.

Adult↗
PubMed2004

Radial glia give rise to adult neural stem cells in the subventricular zone.

Neural stem cells with the characteristics of astrocytes persist in the subventricular zone (SVZ) of the juvenile and adult brain. These cells generate large numbers of new neurons that migrate through the rostral migratory stream to the olfactory bulb. The developmental origin of adult neural stem cells is not known. Here, we describe a lox-Cre-based technique to specifically and permanently label a restricted population of striatal radial glia in newborn mice. Within the first few days after labeling, these radial glial cells gave rise to neurons, oligodendrocytes, and astrocytes, including astrocytes in the SVZ. Remarkably, the rostral migratory stream contained labeled migratory neuroblasts at all ages examined, including 150-day-old mice. Labeling dividing cells with the S-phase marker BrdUrd showed that new neurons continue to be produced in the adult by precursors ultimately derived from radial glia. Furthermore, both radial glia in neonates and radial glia-derived cells in the adult lateral ventricular wall generated self-renewing, multipotent neurospheres. These results demonstrate that radial glial cells not only serve as progenitors for many neurons and glial cells soon after birth but also give rise to adult SVZ stem cells that continue to produce neurons throughout adult life. This study identifies and provides a method to genetically modify the lineage that links neonatal and adult neural stem cells.

Aging↗
PubMed1989

Stochastic model for multipotent hemopoietic progenitor differentiation.

In this study, the authors propose a stochastic model for multipotent hemopoietic progenitor differentiation, which assumes that there is a fixed probability (P) that a progenitor with a potential for differentiation along a particular lineage maintains the potential in each cell division in each daughter cell, and this differentiation process of each lineage proceeds independently. To examine the applicability of this model, a sequential micromanipulation of paired progenitors was carried out and followed by cytological examination of the cells contained in the colonies derived from these progenitors; then calculation was made of the ratio of the number of paired colonies containing cell(s) with a particular lineage to the number of paired colonies in which only one colony contained cell(s) with the lineage at the first and second cell division. The ratios were similar at the first and second cell division within each lineage. Furthermore, the frequences of each lineage in multilineage hemopoietic colonies were calculated using the P values obtained from these micromanipulation experiments. The expected frequencies were similar to those in the actual experiments. These results suggested that the stochastic model was applicable to multipotent hemopoietic progenitor differentiation.

Cell Differentiation↗
PubMed1992

A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.

The mitogenic actions of epidermal growth factor (EGF) were examined in low-density, dissociated cultures of embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation of single progenitor cells that began to divide between 5 and 7 d in vitro, and after 13 d in vitro had formed a cluster of undifferentiated cells that expressed nestin, an intermediate filament present in neuroepithelial stem cells. In the continued presence of EGF, cells migrated from the proliferating core and differentiated into neurons and astrocytes. The actions of EGF were mimicked by the homolog transforming growth factor alpha (TGF alpha), but not by NGF, basic fibroblast growth factor, platelet-derived growth factor, or TGF beta. In EGF-generated cultures, cells with neuronal morphology contained immunoreactivity for GABA, substance P, and methionine-enkephalin, three neurotransmitters of the adult striatum. Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor. These findings suggest that EGF and/or TGF alpha may act on a multipotent progenitor cell in the striatum to generate both neurons and astrocytes.

Animals↗
PubMed2000

Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain.

Human neural stem cells (HNSCs) may serve as a cellular vehicle for molecular therapies as well as for cell replacement in the human CNS. The survival, integration, and differentiation of HNSC.100, a multipotent cell line of HNSCs (A. Villa et al. (2000), Exp. Neurol. 161, 67-84), conditionally perpetuated by genetic and epigenetic means, was investigated after transplantation to the striatum and substantia nigra of the adult, intact rat brain. These are two key regions in the mammalian brain involved in the control of voluntary movement and motor coordination, among other functions. Soon after transplantation (1 week), the cells had already integrated in a nondisruptive manner into the surrounding tissue and migrated out of the implantation site to different distances depending on graft location (in the range of 0.5-2.5 mm). Cell migration was markedly more extensive in the striatum, where the cells colonized the whole extent of the caudate-putamen, than in the substantia nigra region. The engrafted cells completely downregulated the stem cell marker nestin and, due to their multipotential nature, differentiated and expressed mature neural markers. As expected from cells grafted into nonneurogenic regions of the intact brain, the majority of differentiated cells expressed GFAP (astroglia), but expression of other markers, like GalC (oligodendroglia) and MAP2, beta-tubulin III, NeuN, and NSE (for mature neurons) could also be detected. These results demonstrate that genetically perpetuated HNSCs, once transplanted, find residence in the host brain, where they differentiate, generating mature neural cells in the host, chimeric, adult mammalian brain. HNSCs cell lines may be a highly useful model for the development of humanized systems for cell replacement and/or gene transfer to the CNS, which will likely be strong candidates for future therapeutic application in human neurodegenerative conditions.

Animals↗
PubMed2002

A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells.

Purmorphamine, which is a 2,6,9-trisubstituted purine compound, was discovered through cell-based high-throughput screening from a heterocycle combinatorial library. It differentiates multipotent mesenchymal progenitor cells into an osteoblast lineage. It will serve as a unique chemical tool to study the molecular mechanisms of osteogenesis of stem cells and bone development.

Alkaline Phosphatase↗