PDGF receptors on cells of the oligodendrocyte-type-2 astrocyte (O-2A) cell lineage

Development ◽  
1989 ◽  
Vol 105 (3) ◽  
pp. 595-603 ◽  
Author(s):  
I.K. Hart ◽  
W.D. Richardson ◽  
C.H. Heldin ◽  
B. Westermark ◽  
M.C. Raff
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Human Fibroblasts ◽  
Cell Lineage ◽  
Pdgf Receptor ◽  
Oligodendrocyte Differentiation ◽  
Oligodendrocyte Development

It has been shown previously that cultures of rat optic nerve contain three types of macroglial cells—oligodendrocytes and two types of astrocytes. Type-1 astrocytes develop from their own precursor cells beginning before birth, while oligodendrocytes and type-2 astrocytes develop postnatally from a common bipotential precursor called the O-2A progenitor cell. Proliferating O-2A progenitor cells give rise to postmitotic oligodendrocytes beginning around birth, and to type-2 astrocytes beginning in the second postnatal week. Studies in vitro have suggested that platelet-derived growth factor (PDGF), secreted by type-1 astrocytes, plays an important part in timing oligodendrocyte development: PDGF seems to keep O-2A progenitor cells proliferating until an intrinsic clock in the progenitor cells initiates the process leading to oligodendrocyte differentiation. The clock apparently determines when a progenitor cell becomes unresponsive to PDGF, at which point the cell stops dividing and, as a consequence, automatically differentiates into an oligodendrocyte. Here we have used radiolabelled PDGF to show that O-2A progenitor cells have PDGF receptors, suggesting that these cells respond directly to PDGF. The receptors resemble the type A PDGF receptor previously described on human fibroblasts and are initially retained when progenitor cells stop dividing and develop in vitro into oligodendrocytes. The latter finding indicates that receptor loss is not the reason that progenitor cells initially become mitotically unresponsive to PDGF.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals PDGF and intracellular signaling in the timing of oligodendrocyte differentiation.

1989 ◽  
Vol 109 (6) ◽  
pp. 3411-3417 ◽  
Author(s):  
I K Hart ◽  
W D Richardson ◽  
S R Bolsover ◽  
M C Raff
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Intracellular Signaling ◽  
Progenitor Cell ◽  
Receptor Activation ◽  
Oligodendrocyte Differentiation ◽  
Intracellular Signaling Pathways ◽  
Parsimonious Explanation ◽  
Oligodendrocyte Development

In the rat optic nerve, bipotential O-2A progenitor cells give rise to oligodendrocytes and type 2 astrocytes on a precise schedule. Previous studies suggest that PDGF plays an important part in timing oligodendrocyte development by stimulating O-2A progenitor cells to proliferate until they become mitotically unresponsive to PDGF, stop dividing, and differentiate automatically into oligodendrocytes. Since the loss of mitotic responsiveness to PDGF has been shown not to be due to a loss of PDGF receptors, we have now examined the possibility that the unresponsiveness results from an uncoupling of these receptors from early intracellular signaling pathways. We show that (a) although PDGF does not stimulate newly formed oligodendrocytes to synthesize DNA, it induces an increase in cytosolic Ca2+ in these cells; (b) a combination of a Ca2+ ionophore plus a phorbol ester mimics the effect of PDGF, both in stimulating O-2A progenitor cell division and in reconstituting the normal timing of oligodendrocyte differentiation in culture; and (c) the same combination of drugs does not stimulate newly formed oligodendrocytes to proliferate, even in the presence of PDGF or dibutyryl cAMP. The most parsimonious explanation for these results is that O-2A progenitor cells become mitotically unresponsive to PDGF because the intracellular signaling pathways from the PDGF receptor to the nucleus are blocked downstream from the receptor and some of the early events that are triggered by receptor activation.

scholarly journals A role for TGF-beta in oligodendrocyte differentiation.

1993 ◽  
Vol 121 (6) ◽  
pp. 1397-1407 ◽  
Author(s):  
R D McKinnon ◽  
G Piras ◽  
J A Ida ◽  
M Dubois-Dalcq
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Tgf Beta ◽  
Oligodendrocyte Differentiation ◽  
Progenitor Cell Proliferation ◽  
Glial Progenitor Cells ◽  
Oligodendrocyte Development ◽  
Oligodendrocyte Cultures

Oligodendrocyte-type-2 astrocyte (O-2A) glial progenitor cells undergo a limited number of mitotic divisions in response to PDGF before differentiating into oligodendrocytes, the myelin-forming cell of the CNS. We examined the mechanism limiting O-2A proliferation, and demonstrate that these cells secrete an inhibitor of cell proliferation that can be neutralized with antibodies to TGF-beta. O-2A cells also secrete an inhibitory activity that cannot be neutralized with TGF-beta antibodies. O-2A progenitor cultures express TGF-beta 1 isoform and its transcript, while oligodendrocyte cultures express TGF-beta 1, beta-2, and beta-3 isoforms. Both recombinant TGF-beta 1 and O-2A conditioned medium inhibit the proliferation of O-2A progenitor cells cultured in the presence of PDGF, and this inhibition can be partially neutralized with polyclonal TGF-beta antibodies. Thus, TGF-beta produced by O-2A cells may limit PDGF-driven mitosis and promote oligodendrocyte development. TGF-beta is a less potent inhibitor of O-2A proliferation when these cells are cultured in the presence of bFGF, suggesting that bFGF interferes with TGF-beta signaling. Thus, the production of TGF-beta by cells in the O-2A lineage may account for the distinct effects of PDGF and bFGF on O-2A progenitor cell proliferation. Moreover, our results suggest that TGF-beta may be an important mediator of oligodendrocyte differentiation.

scholarly journals Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development.

1990 ◽  
Vol 111 (2) ◽  
pp. 635-644 ◽  
Author(s):  
L E Lillien ◽  
M Sendtner ◽  
M C Raff
Keyword(s):  
Extracellular Matrix ◽  
Progenitor Cells ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Oligodendrocyte Differentiation ◽  
Stable Type ◽  
Extracellular Signals ◽  
Astrocyte Differentiation

O-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serum-free cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on O-2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibiting oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

scholarly journals Effect of Different Fermentation Condition on Estimated Glycemic Index, In Vitro Starch Digestibility, and Textural and Sensory Properties of Sourdough Bread

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 514
Author(s):  
Hilal Demirkesen-Bicak ◽  
Muhammet Arici ◽  
Mustafa Yaman ◽  
Salih Karasu ◽  
Osman Sagdic
Keyword(s):  
Glycemic Index ◽  
Sensory Properties ◽  
Starch Digestibility ◽  
In Vitro Starch Digestibility ◽  
Whole Wheat ◽  
Sourdough Bread ◽  
Estimated Glycemic Index

This study aimed to evaluate the influence of sourdough fermentation on the estimated glycemic index (eGI), in vitro starch digestibility, and textural and sensory properties of eight experimentally prepared sourdough breads. Wheat and whole wheat flour bread samples were produced under different fermentation conditions (25 °C and 30 °C) and fermentation methods (type-1 and type-2). In type-1 fermentation, sourdough was obtained via spontaneous fermentation. Indigenous strains (Lactobacillus brevis ELB99, Lactiplantibacillus plantarum ELB75, and Saccharomyces cerevisiae TGM55) were used for type-2 fermentation. Fermentation type and temperature significantly affected eGI, the hydrolysis index (HI), the starch fraction, and the textural properties of the samples (p < 0.05). The resistant starch (RS) content increased after fermentation, while rapidly digestible starch (RDS), HI, and eGI decreased. RS values were significantly higher in type-2 than in type-1 at the same temperature for both flour types (p < 0.05). At 25 °C, RS values were higher in both fermentation types. In the white flour samples, eGI values were in the range of 60.8–78.94 and 62.10–78.94 for type-1 and type-2, respectively. The effect of fermentation type on eGI was insignificant (p < 0.05). In the whole flour samples, fermentation type and temperature significantly affected eGI (p < 0.05). The greatest eGI decreases were in whole wheat sourdough bread at 30 °C using type-2 (29.74%). The 30 °C and type-2 samples showed lower hardness and higher specific volume. This study suggests that fermentation type and temperature could affect the eGI and the textural and sensory properties of sourdough bread, and these factors should be considered during bread production. The findings also support the consumption of wheat and whole wheat breads produced by type-2 fermentation due to higher RS and slowly digestible starch (SDS) and lower RDS and eGI values.

scholarly journals First Report ofEurycoma longifoliaJack Root Extract Causing Relaxation of Aortic Rings in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Bae Huey Tee ◽  
See Ziau Hoe ◽  
Swee Hung Cheah ◽  
Sau Kuen Lam
Keyword(s):  
Erectile Function ◽  
Receptor Activation ◽  
Root Extract ◽  
Ang Ii ◽  
Angiotensin I ◽  
Eurycoma Longifolia ◽  
Vasodilatory Effect

AlthoughEurycoma longifoliahas been studied for erectile function, the blood pressure- (BP-) lowering effect has yet to be verified. Hence, this study aims at investigating the BP-lowering properties of the plant with a view to develop an antihypertensive agent that could also preserve erectile function. Ethanolic root extract was partitioned by hexane, dichloromethane (DCM), ethyl acetate, butanol, and water. The DCM fraction, found to be potent in relaxing phenylephrine- (PE-) precontracted rat aortic rings, was further purified by column chromatography. Subfraction DCM-II, being the most active in relaxing aortae, was studied for effects on the renin-angiotensin and kallikrein-kinin systems in aortic rings. The effect of DCM-II on angiotensin-converting enzyme (ACE) activity was also evaluatedin vitro. Results showed that DCM-II reduced (p<0.05) the contractions evoked by angiotensin I and angiotensin II (Ang II). In PE-precontracted rings treated with DCM-II, the Ang II-induced contraction was attenuated (p<0.05) while bradykinin- (BK-) induced relaxation enhanced (p<0.001).In vitro, DCM-II inhibited (p<0.001) the activity of ACE. These data demonstrate that the vasodilatory effect of DCM-II appears to be mediatedviainhibition of Ang II type 1 receptor and ACE as well as enhancement of Ang II type 2 receptor activation and BK activity.

scholarly journals Differential Activation of CD8+Tumor-Specific Tc1 and Tc2 Cells by an IL-10-Producing Murine Plasmacytoma

1998 ◽  
Vol 6 (3-4) ◽  
pp. 331-342 ◽  
Author(s):  
Christoph Specht ◽  
Hans-Gerd Pauels ◽  
Christian Becker ◽  
Eckehart Kölsch
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
T Cell Subsets ◽  
Early Stages ◽  
Specific Tolerance

The involvement of counteractiveCD8+T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model.CD8+Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cellsin vivoandin vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance, but depends on the induction of tumor-specific tolerance, involving a population of tumorinducedCD8+T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-γas a suppressive factor. Whereas most longterm cultivated CD8+ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primaryin vitroTc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10.CD8+Tc cells that are induced in a primary MLTC do not produce IFN-γ, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-γor IL-12. In contrast, ADJ-PC- 5-specificCD8+Tc cells from immunized mice are IFN-γproducing Tc1 cells. Since the primaryin vitroTc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-γthese Tc1 cells behave similar to the suppressiveCD8+T cells that are induced during early stages of ADJ-PC-5 tumorigenesis.

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