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Results for “Multipotent Stem Cells”

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At least 19 recordsLinked to original sources

PubMed2000

Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells.

Multipotent stem cells that generate both neurons and glia are widespread components of the early neuroepithelium. During CNS development, neurogenesis largely precedes gliogenesis: how is this timing achieved? Using clonal cell culture combined with long-term time-lapse video microscopy, we show that isolated stem cells from the embryonic mouse cerebral cortex exhibit a distinct order of cell-type production: neuroblasts first and glioblasts later. This is accompanied by changes in their capacity to make neurons versus glia and in their response to the mitogen EGF. Hence, multipotent stem cells alter their properties over time and undergo distinct phases of development that play a key role in scheduling production of diverse CNS cells.

Animals↗

PubMed1983

The origin of human B and T cells from multipotent stem cells: a study of the Tn syndrome.

The Tn (or polyagglutinability) syndrome corresponds to a human nonmalignant acquired condition which results from a somatic mutation occurring at the level of bone marrow stem cells. This model offers therefore a unique opportunity to study the contribution of multipotential stem cells to the maintenance of cells from the lymphoid lineage. We found that the Tn mutation is expressed by both myeloid and lymphoid mature blood cells. Whereas a large proportion of surface IgM-bearing B cells carry the Tn mutation, only a small percentage of T cells and IgA- or IgG-bearing B cells are defective, showing that under physiological conditions the penetration of stem cells into the various myeloid and lymphoid compartments is variable.

ABO Blood-Group System↗

PubMed2001

Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin.

In skin, multipotent stem cells generate the keratinocytes of the epidermis, sebaceous gland, and hair follicles. In this paper, we show that Tcf3 and Lef1 control these differentiation lineages. In contrast to Lef1, which requires Wnt signaling and stabilized beta-catenin to express the hair-specific keratin genes and control hair differentiation, Tcf3 can act independently of its beta-catenin interacting domain to suppress features of epidermal terminal differentiation, in which Tcf3 is normally shut off, and promote features of the follicle outer root sheath (ORS) and multipotent stem cells (bulge), the compartments which naturally express Tcf3. These aspects of Tcf3's action are dependent on its DNA binding and Groucho repressor-binding domains. In the absence of its beta-catenin interacting domain, Lef1's behavior (Delta NLef1) seems to be markedly distinct from that of Delta NTcf3. Delta NLef1 does not suppress epidermal differentiation and promote ORS/bulge differentiation, but rather suppresses hair differentiation and gives rise to sebocyte differentiation. Taken together, these findings provide powerful evidence that the status of Tcf3/Lef complexes has a key role in controlling cell fate lineages in multipotent skin stem cells.

Animals↗

PubMed2002

Stem cells in the treatment of Parkinson's disease.

Stem cells have been suggested as candidate therapeutic tools for neurodegenerative disorders, given their ability to give rise to the appropriate cell types after grafting in vivo. In this review I summarize some of the evidence currently available concerning two approaches for the treatment of Parkinson's disease: (1) The generation of dopaminergic neurons from embryonic stem cells, multipotent stem cells, and neuronal progenitor cells for cell replacement therapy. (2) The engineering of multipotent stem cells to release glial cell-line derived neurotrophic factor, a potent neurotrophic factor for dopaminergic neurons, in a neuroprotective and neuroregenerative approach to the treatment of Parkinson's disease.

Animals↗

PubMed2002

[Long-term culture of dermis-derived multipotent stem cells and the effects of collagen sponge on their growth in vitro].

Autologous multipotent stem cells are most relevant cells for regenerative medicine and show prosperous future in the treatment of human diseases. Previous reports have indicated that multipotent stem cells (MSCs) can be obtained from bone marrow and adipose tissues. In this study, we proved that dermis may be another source of these cells. MSCs were isolated from the dermis of newborn rats one day old by adhesion competition and successive culture. These cells conserved the ability to differentiate to osteoblasts, chondrocytes and adipocytes by induction media containing dexamethasone. After long term of more than 6 months, till 25th generation, the cells still maintained the characteristics of stem cells: high activity of self-renewal and multipotency. Mixed collagen matrix from dermis could promote the growth of dermis-derived multipotent stem cells and collagen sponge stent could promote their three-dimensional growth in vitro.

Animals↗

PubMed1979

Control of nerve cell formation from multipotent stem cells in Hydra.

Feeding of starved animals provides a very short signal which determines stem cells to differentiate into nerve cells after the next mitosis. Only those stem cells become determined which are just in the middle of their S-phase at the time of feeding. Stem cells of any other stage of the cycle do not become determined. Nerve cell determination is suppressed by very low concentrations of an endogenous inhibitor. The inhibitor exerts its effect only during the first half of the S-phase, not before and not after this period. Based on these finding it is proposed that stem cells are susceptible to 2 different signals during the first half of their S-phase; one signal allows the development into nerve cells, the other prevents this development. Within this period the decision whether to become a nerve cell or not is reversible. It becomes fixed at the end of this period.

Animals↗

PubMed1992

Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction.

At least fourteen epithelial cell types of the mammalian nephron develop from the metanephric mesenchyme. To distinguish whether this single embryological primordium contains a heterogenous population of committed renal cell lines or a multipotent stem cell, the lac-Z gene was introduced into individual renal progenitors by retroviral mediated gene transfer. The differentiated fate of lac-Z-tagged daughters derived from single metanephric mesenchymal cells was characterized after cytodifferentiation. We found that the metanephric mesenchyme contains multipotent stem cells that can generate at least three distinct cell types; glomerular, proximal and distal epithelia. After induction the fate of this multipotent cell becomes restricted to populate a single nephron segment.

Animals↗

PubMed1980

[Humoral factors in the regulation of cell proliferation in haematopoiesis. II. Erythropoiesis, megakaryopoiesis, multipotent stem cell (author's transl)].

Diffusible factors probably play an important role in the control of cell proliferation during haematopoiesis. Several stimulators of erythropoiesis including erythropoietin are to be found in sera. Inhibitors are found in erythrocyte supernatants, in the urin of newborn children, and in plasma of patients with renal insufficiency. Stimulators of megakaryopoiesis have been shown to be present in conditioned media of lymphoid cells and bone marrow cells. Inhibitors have been detected in various sera. Proliferation of multipotent stem cells is probably also regulated by a humoral mechanism. Stimulators and inhibitors are present in bone marrow extracts. Clinical relevance of these factors is discussed.

Cell Division↗

PubMed1983

Chronic myelomonocytic leukemia with a chromosome abnormality (46,XY,20q-) in all dividing myeloid cells: evidence for clonal origin in a multipotent stem cell common to granulocyte, monocyte, erythrocyte, and thrombocyte.

In a typical case of chronic myelomonocytic leukemia (CMML), a chromosome abnormality, 46,XY,20q-, was observed in all the dividing cells including up to 16-ploid cells in the bone marrow and the blood. As the mitotic figures could be easily seen not only in myelomonocytoid cells but also in erythroblasts in the bone marrow smear, it was concluded that all the cell lineages except lymphocytes had the abnormality. The present case will support the view that the leukemic process in CMML affects a multipotent stem cell rather than a granulocyte-monocyte committed stem cell.

Aged↗

PubMed2001

Morphogenesis and renewal of hair follicles from adult multipotent stem cells.

The upper region of the outer root sheath of vibrissal follicles of adult mice contains multipotent stem cells that respond to morphogenetic signals to generate multiple hair follicles, sebaceous glands, and epidermis, i.e., all the lineages of the hairy skin. At the time when hair production ceases and when the lower region of the follicle undergoes major structural changes, the lower region contains a significant number of clonogenic keratinocytes, and can then respond to morphogenetic signals. This demonstrates that multipotent stem cells migrate to the root of the follicle to produce whisker growth. Moreover, our results indicate that the clonogenic keratinocytes are closely related, if not identical, to the multipotent stem cells, and that the regulation of whisker growth necessitates a precise control of stem cell trafficking.

Animals↗

PubMed2001

Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis.

During CNS development, cell migrations play an important role, adding to the cellular complexity of different regions. Earlier studies have shown a robust migration of cells from basal forebrain into the overlying dorsal forebrain during the embryonic period. These immigrant cells include GABAergic neurons that populate the cerebral cortex and hippocampus. In this study we have examined the fate of other basal forebrain cells that migrate into the dorsal forebrain, identifying basal cells using an antibody that recognizes both early (dlx1/2) and late (dlx 5/6) members of the dlx homeobox gene family. We found that a subpopulation of cortical and hippocampal oligodendrocytes are also ventral-derived. We traced the origin of these cells to basal multipotent stem cells capable of generating both GABAergic neurons and oligodendrocytes. A clonal analysis showed that basal forebrain stem cells produce significantly more GABAergic neurons than dorsal forebrain stem cells from the same embryonic age. Moreover, stem cell clones from basal forebrain are significantly more likely to contain both GABAergic neurons and oligodendrocytes than those from dorsal. This indicates that forebrain stem cells are regionally specified. Whereas dlx expression was not detected within basal stem cells growing in culture, these cells produced dlx-positive products that are capable of migration. These data indicate that the developing cerebral cortex incorporates both neuronal and glial products of basal forebrain and suggest that these immigrant cells arise from a common progenitor, a dlx-negative basal forebrain stem cell.

Animals↗

PubMed2003

Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development.

Class I homeobox (HOX) genes comprise a large family of transcription factors that have been implicated in normal and malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degenerated RT-PCR and Affymetrix microarray analysis, we analyzed the expression pattern of this gene family in human multipotent stem cells from fetal liver (FL) and adult bone marrow (ABM), and in T-cell progenitors from child thymus. We show that FL and ABM stem cells are similar in terms of HOX gene expression, but significant differences were observed between these two cell types and child thymocytes. As the most immature thymocytes are derived from immigrated FL and ABM stem cells, this indicates a drastic change in HOX gene expression upon entry into the thymus. Further analysis of HOX-A7, HOX-A9, HOX-A10, and HOX-A11 expression with specific RT-PCR in all thymocyte differentiation stages showed a sequential loss of 3' region HOX-A cluster genes during intrathymic T-cell development and an unexpected expression of HOX-A11, previously not recognized to play a role in hematopoiesis. Also HOX-B3 and HOX-C4 were expressed throughout thymocyte development. Overall, these data provide novel evidence for an important role of certain HOX genes in human T-cell development.

Adult↗

PubMed1988

Molecularly characterized factors governing the growth of murine multipotent stem cells in serum-depleted marrow cultures.

The growth requirements of normal murine marrow-derived multipotent stem cells (CFU-GEMM) in a simple clonal cell culture system substantially devoid of exogenous serum proteins was assessed. The ability of murine interleukin-3 (Il-3), recombinant human erythropoietin (rEPO), and a crystalline preparation of the protoporphyrin hemin to support colony growth in "serum-free" cultures was examined by titration. The results suggest that both Il-3 and hemin are limiting for multipotential colony growth in "serum-free" cultures, but that EPO is not. In addition, the 'sensitivity' of CFU-GEMM to each growth factor appeared to increase in the "serum-free" environment as evidenced by a "shift-to-the-left" in all the titration curves. Nearly half of the GEMM colonies grew to full maturity in the absence of exogenous EPO. Given the optimal concentration of each growth factor, high colony growth was consistently observed in the "serum-free" cultures, with a range from 65% to 119% of the serum control level. It is therefore concluded that supplementation of murine marrow cultures with Il-3 and hemin alone may provide the necessary setting for studying the factors which modulate the growth of multipotent stem cells in a serum-free environment.

Animals↗

PubMed2002

Properties of a fetal multipotent neural stem cell (NEP cell).

Multipotent neural stem cells (NSCs) present in the developing neural tube (E10.5, neuroepithelial cells; NEP) were examined for the expression of candidate stem cell markers, and the expression of these markers was compared with later appearing precursor cells (E14.5) that can be distinguished by the expression of embryonic neural cell adhesion molecule (E-NCAM) and A2B5. NEP cells possess gap junctions, express connexins, and appear to lack long cilia. Most candidate markers, including Nestin, Presenilin, Notch, and Numb, were expressed by both NEP cells as well as other cell populations. Fibroblast growth factor receptor 4 (FGFR4), Frizzled 9 (Fz9), and SRY box-containing gene 2 (Sox2) as assessed by immunocytochemistry and in situ hybridization are markers that appear to distinguish NSCs from other precursor cells. Neither Hoechst 33342 nor rhodamine-123 staining, telomerase (Tert) expression, telomerase activity, or breakpoint cluster region protein 1 (Bcrp1) transporter expression could be used to distinguish NEP stem cells from other dividing cells. NEP cells, however, lacked expression of several lineage markers that are expressed by later appearing cells. These included absence of expression of CD44, E-NCAM, A2B5, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor-alpha (PDGFR alpha), suggesting that negative selection using cell surface epitopes could be used to isolate stem cell populations from mixed cultures of cells. Using mixed cultures of cells isolated from E14.5 stage embryos, we show that NEP cells can be enriched by depleting differentiating cells that express E-NCAM or A2B5 immunoreactivity. Overall, our results show that a spectrum of markers used in combination can reliably distinguish multipotent NSCs from other precursor cells as well as differentiated cells present in the CNS.

Acetylcholine↗

PubMed1988

Multipotent stem cell (CFU-S) numbers and circadian variations in aging mice.

The multipotent stem cell (CFU-S) numbers were studied in aging female C3H mice (16, 21 and 26 months old, respectively) versus young controls (3 months old). Using the spleen colony technique, the d-8 CFU-S numbers were measured every 3 h during the 24-h period at three different times of the year. Prominent circadian variations were found in young mice. The peak and trough values were significantly different also in aging mice, although the peak-trough differences were declining. When comparing young and old mice at different times of the 24-h period, the CFU-S numbers were sometimes significantly different, but often not. The 24-h mean values were consistently declining during aging. Young mice had different circadian variation patterns and 24-h mean values when examined at different times of the year. It is concluded that the d-8 CFU-S numbers decline in aging mice. Conflicting reports may partly be due to neglect of physiological variations.

Aging↗

PubMed1988

Growth of murine multipotent stem cells in a simple "serum-free" culture system: role of interleukin-3, erythropoietin, and hemin.

The growth requirements of normal murine marrow-derived multipotent stem cells (CFU-GEMM) in a simple clonal cell culture system substantially devoid of exogenous serum proteins was assessed. The ability of murine interleukin-3 (Il-3), recombinant human erythropoietin (rEPO), and a crystalline preparation of the protoporphyrin hemin to support colony growth in "serum-free" cultures was examined by titration. The results suggest that both Il-3 and hemin are limiting for multipotential colony growth in "serum-free" cultures, but that EPO is not. In addition, the "sensitivity" of CFU-GEMM to each growth factor appeared to increase in the "serum-free" environment as evidenced by a "shift-to-the-left" in all the titration curves. Nearly half of the GEMM colonies grew to full maturity in the absence of exogenous EPO. Given the optimal concentration of each growth factor, high colony growth was consistently observed in the "serum-free" cultures, with a range from 65% to 119% of the serum control level. It is therefore concluded that supplementation of murine marrow cultures with Il-3 and hemin alone may provide the necessary setting for studying the factors that modulate the growth of multipotent stem cells in a serum-free environment.

Animals↗

PubMed1981

Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell.

Essential thrombocythemia is characterized by proliferation of hematopoietic tissue predominantly involving megakaryocytes and resulting in marked thrombocytosis. The disorder has some clinical and laboratory features that resemble those seen in the clonal multipotent stem cell disorders chronic myelogenous leukemia, polycythemia vera, and agnogenic myeloid metaplasia. It has been argued that essential thrombocythemia should be classified together with those disorders as a myeloproliferative syndrome. However, without knowledge of the numbers and types of cells that are involved in essential thrombocythemia, this suggestion remains speculative. Three patients with thrombocytosis were studied. The diagnosis of essential thrombocythemia was considered to be firm in two patients and probable in the third one. The X-linked glucose-6-phosphate dehydrogenase locus was used as a cell marker. Whereas both A and B types of glucose-6-phosphate dehydrogenase were found in nonhematopoietic tissues, only a single-enzyme type was found in the granulocytes, red cells, and platelets from each patient. These data indicate that the disorders in these three patients are clonal and involve multipotent stem cells.

Adult↗

PubMed1980

Philadelphia chromosome (Ph1)-negative chronic myelogenous leukemia (CML): a clonal disease with origin in a multipotent stem cell.

It has been shown with glucose 6-phosphate dehydrogenase (G-6-PD) mosaicism that Ph1-positive chronic myelogenous leukemia (CML) is a clonal disease that involves multipotent hematopoietic stem cells. We now report G-6-PD studies of a 79-yr-old woman with Ph1-negative CML. Equal amounts of B and A-type activities were found in nonhematopoietic tissues, indicating that the patient was heterozygous for G-6-PD. In contrast, only A-type G-6-PD was found in marrow cells, blood erythrocytes, leukocytes, and platelets and in granulocyte-monocyte and eosinophil colonies grown from blood mononuclear cells. Unlike most cases of PH1-positive CML, colony growth in this patient increased during blastic transformation and the colonies contained only immature monocytic cells. The data indicate that in this patient, Ph1-negative CML is similar to the Ph1-positive form of the disease in involvement of multipotent stem cells and probable clonal origin, but the two disorders differ in the rapidity with which they enter blastic transformation and in the pattern of granulocyte-monocyte colony growth at that time.

Aged↗