A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 947-957 ◽  
Author(s):  
D. Altshuler ◽  
C. Cepko
Keyword(s):  
Cell Fate ◽  
Rod Photoreceptor ◽  
Cell Type ◽  
Retinal Neuron ◽  
Development In Vitro ◽  
Temporally Correlated ◽  
Photoreceptor Development

The retina is a relatively simple and well-characterized CNS structure in which cell-cell interactions have been hypothesized to influence cell type determination. By manipulating cell density in serum-free cultures we show that rat rod photoreceptor development requires a diffusible activity produced by neonatal retinal cells. This effect is not mediated by changes in cell survival or mitosis. Production of the rod promoting activity varies with developmental stage and is temporally correlated with the timing of rod generation in vivo. In low density cultures, which do not support rod development, an increased fraction of cells stain with an antibody specific for another retinal neuron, the bipolar cell. Thus, the diffusible rod promoting activity may influence cell fate determination, and not only terminal differentiation. These results provide an approach for the molecular characterization of developmentally important signals in the vertebrate retina.

Taurine promotes the differentiation of a vertebrate retinal cell type in vitro

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1317-1328 ◽  
Author(s):  
D. Altshuler ◽  
J.J. Lo Turco ◽  
J. Rush ◽  
C. Cepko
Keyword(s):  
Conditioned Medium ◽  
Control Cell ◽  
Retinal Cell ◽  
Rod Photoreceptor ◽  
Cell Type ◽  
Retinal Explants ◽  
Development In Vitro ◽  
Photoreceptor Development

The retina offers a model system for investigating the mechanisms that control cell type determination and differentiation in the vertebrate central nervous system. Previously, rod photoreceptor development in vitro was found to require a diffusible activity released by retinal cells (D. Altshuler and C. Cepko, Development 114, 947–957, 1992). In this report, we show that retinal-cell-conditioned medium and extracts contain two separable activities that influence rod development: a > 10 kDa inhibitory activity, and a stimulatory activity that is < 1 kDa and heat stable. Taurine was found to be a component of the < 1 kDa fraction and to stimulate rod development when added to retinal cultures. Taurine was not the only rod-promoting factor in these retinal preparations, however, as conditioned medium and extracts stimulated a higher level of rod development than did taurine alone. Taurine uptake into cells could be blocked without inhibiting taurine's ability to stimulate rod development, arguing against an osmoregulatory or nutritive mechanism of action. Finally, a competitive antagonist of taurine's bioactivity was identified and shown partially to inhibit rod development in retinal explants, suggesting that taurine may normally act to stimulate rod development in the retina. These results provide evidence for three activities, one of which is taurine, that are candidate regulators of rod photoreceptor development in vivo.

Development, in-vitro and in-vivo characterization of gelatin nanoparticles for delivery of an anti-inflammatory drug

2016 ◽  
Vol 36 ◽  
pp. 55-61 ◽  
Author(s):  
Alok Mahor ◽  
Sunil Kumar Prajapati ◽  
Amita Verma ◽  
Rishikesh Gupta ◽  
Thakur Raghu Raj Singh ◽  
...  
Keyword(s):  
Gelatin Nanoparticles ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Development In Vitro ◽  
In Vivo Characterization

scholarly journals Development, in vitro and in vivo evaluations of novel lipid drug delivery system of Newbouldia laevis (P. Beauv.)

2016 ◽  
Vol 3 ◽  
pp. 184954351667344
Author(s):  
Chukwuebuka Umeyor ◽  
Emmanuel Anaka ◽  
Franklin Kenechukwu ◽  
Chinazom Agbo ◽  
Anthony Attama
Keyword(s):  
Encapsulation Efficiency ◽  
Folk Medicine ◽  
Research Work ◽  
Lipid Matrix ◽  
Solid Lipid ◽  
Development In Vitro

Newbouldia laevis (P. Beauv.) is a tropical rainforest plant used in traditional folk medicine for the treatment of malaria, cough, joint pains, stomach ache, oedema and inflammation. The main thrust of this research work was to study the analgesic/anti-nociceptive properties of N. laevis-loaded solid lipid microdispersions. N. laevis leaves were extracted using ethanol, and the extract was formulated into solid lipid microdispersions using lipid matrix comprising a rational blend of Precirol® ATO 5 and Softisan® 154. Characterization of the solid lipid microdispersions include determination of morphology, particle size, pH, thermal property, encapsulation efficiency percentage and analgesic/anti-nociceptive property. The results obtained showed that the particles were spherical with sizes ranging from 40 µm to 125 µm. The solid lipid microdispersions maintained a stable pH within the acidic region of 5–6 with insignificant variations ( p > 0.05) over a period of 90 days. Thermal analysis showed that N. laevis was entrapped in the lipid matrix used for the formulations. Solid lipid microdispersions recorded a maximum encapsulation efficiency up to 88.1%. N. laevis-loaded solid lipid microdispersions also produced good analgesic/anti-nociceptive property comparable with the standard diclofenac potassium. N. laevis-loaded solid lipid microdispersions showed good analgesic/anti-nociceptive effect and could be used in the treatment and management of pain.

Ciliary neurotrophic factor promotes chick photoreceptor development in vitro

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2695-2706 ◽  
Author(s):  
S. Fuhrmann ◽  
M. Kirsch ◽  
H.D. Hofmann
Keyword(s):  
Growth Factor ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Rod Photoreceptor ◽  
Opsin Expression ◽  
Chick Retina ◽  
Continuous Presence ◽  
Development In Vitro ◽  
Photoreceptor Development

Previous in vitro studies have convincingly demonstrated the involvement of diffusible factors in the regulation of photoreceptor development. We now provide evidence that ciliary neurotrophic factor (CNTF) represents one of these regulatory molecules. In low density monolayer cultures prepared from embryonic day 8 chick retina, photoreceptor development was studied using the monoclonal antiopsin antibody rho-4D2 as a differentiation marker. The number of cells acquiring opsin immunoreactivity, determined after 3 days in vitro, was increased up to 4-fold in the presence of CNTF to maximally 10.5% of all cells. Basic fibroblast growth factor or taurine both of which have been reported to stimulate opsin expression in rat retinal cultures and other neurotrophic factors tested (nerve growth factor, brain derived neurotrophic factor) had no effect. The EC50 of the CNTF effect (2.6 pM) was virtually identical to that measured for other CNTF receptor mediated cellular responses. Conditioned medium produced by cultured retinal cells (most likely glial cells) exhibited opsin stimulating activity identical to that of CNTF. Stimulation of opsin expression was specific for morphologically less mature photoreceptors and obviously restricted to rods, since changes in the number of identifiable cone photoreceptors expressing opsin immunoreactivity (10% of all cones) were not detectable. Measurement of the kinetics of the CNTF response revealed that the factor acted on immature opsin-negative progenitors and that CNTF effects were unlikely to reflect enhanced cell survival. Proliferation of photoreceptors was also unaffected, as demonstrated by [3H]thymidine autoradiography. With prolonged culture periods a gradual decrease in the number of opsin-positive cells was observed both in controls and in the continuous presence of CNTF. This decrease could be partly prevented by the addition of 1 mM taurine. Our results suggest that CNTF acted as an inductive signal for uncommitted progenitor cells or during early stages of rod photoreceptor differentiation, whereas other extrinsic stimulatory activities seemed to be required for further maturation.

Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1960-1967 ◽  
Author(s):  
Francis N. Karanu ◽  
Barbara Murdoch ◽  
Tomoyuki Miyabayashi ◽  
Mitsuhara Ohno ◽  
Masahide Koremoto ◽  
...  
Keyword(s):  
Cell Fate ◽  
Hematopoietic Cells ◽  
Functional Roles ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Deficient Mice

Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.

scholarly journals Myeloid translocation gene CBFA2T3 directs a relapse gene program and determines patient-specific outcomes in AML

2019 ◽  
Vol 3 (9) ◽  
pp. 1379-1393 ◽  
Author(s):  
Nickolas Steinauer ◽  
Chun Guo ◽  
Chunfa Huang ◽  
Madeline Wong ◽  
Yifan Tu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Gene Transcription ◽  
Gene Set Enrichment Analysis ◽  
Natural Resistance ◽  
Patient Specific ◽  
Cell Type ◽  
Gene Signatures ◽  
Cell Type Specific

Abstract CBFA2T3 is a master transcriptional coregulator in hematopoiesis. In this study, we report novel functions of CBFA2T3 in acute myeloid leukemia (AML) relapse. CBFA2T3 regulates cell-fate genes to establish gene expression signatures associated with leukemia stem cell (LSC) transformation and relapse. Gene set enrichment analysis showed that CBFA2T3 expression marks LSC signatures in primary AML samples. Analysis of paired primary and relapsed samples showed that acquisition of LSC gene signatures involves cell type–specific activation of CBFA2T3 transcription via the NM_005187 promoter by GCN5. Short hairpin RNA–mediated downregulation of CBFA2T3 arrests G1/S cell cycle progression, diminishes LSC gene signatures, and attenuates in vitro and in vivo proliferation of AML cells. We also found that the RUNX1-RUNX1T1 fusion protein transcriptionally represses NM_005187 to confer t(8;21) AML patients a natural resistance to relapse, whereas lacking a similar repression mechanism renders non–core-binding factor AML patients highly susceptible to relapse. These studies show that 2 related primary AML-associated factors, the expression level of CBFA2T3 and the ability of leukemia cells to repress cell type–specific CBFA2T3 gene transcription, play important roles in patient prognosis, providing a paradigm that differential abilities to repress hematopoietic coregulator gene transcription are correlated with patient-specific outcomes in AML.

Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1960-1967 ◽  
Author(s):  
Francis N. Karanu ◽  
Barbara Murdoch ◽  
Tomoyuki Miyabayashi ◽  
Mitsuhara Ohno ◽  
Masahide Koremoto ◽  
...  
Keyword(s):  
Cell Fate ◽  
Hematopoietic Cells ◽  
Functional Roles ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Deficient Mice

Abstract Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.

Molecular analysis of myc gene mutants

1985 ◽  
Vol 226 (1242) ◽  
pp. 83-92
Keyword(s):  
Acute Leukaemia ◽  
Deletion Mutants ◽  
Wild Type ◽  
Cell Type ◽  
T And B Cells ◽  
Leukaemia Virus ◽  
Myc Gene

We describe the generation and characterization of a series of deletion mutants of the avian acute leukaemia virus MC29 which allow the study of the function of the myc in transformation of quail embryo fibroblasts in vitro and tumour induction in vivo . These mutants, which are deleted in the 3' portion of the myc gene, fail to transform macrophages in vitro or induce tumours in vivo but are still able to transform morphologically fibroblasts. From one of these mutants a ‘recovered’ MC29 virus was generated which, like wild type MC29, transformed fibroblasts and macrophages in vitro . When tested in vivo this virus induced lymphomas of T and B cells rather that the endotheliomas induced by wild type MC29. This system allows us to investigate another question which is the mechanism by which the virus (or oncogene it contains) preferentially transforms one cell type.

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