scholarly journals Loss of active neurogenesis in the adult shark retina

2020 ◽  
Author(s):  
Ismael Hernández-Núñez ◽  
Diego Robledo ◽  
Hélène Mayeur ◽  
Sylvie Mazan ◽  
Laura Sánchez ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Peripheral Retina ◽  
Postnatal Life ◽  
Teleost Fishes ◽  
Rna Seq ◽  
Scyliorhinus Canicula ◽  
Plexiform Layers ◽  
Active Proliferation ◽  
Excellent Resource

AbstractNeurogenesis is the process by which progenitor cells generate new neurons. As development progresses neurogenesis becomes restricted to concrete neurogenic niches, where it persists during postnatal life. The retina of teleost fishes is thought to proliferate and produce new cells throughout life. Whether this capacity may be an ancestral characteristic of jawed vertebrates, shared with chondrichthyans, which diverged from osteichthyans prior to the gnathostome radiation is completely unknown. Previous work from our group revealed that the juvenile retina of the catshark Scyliorhinus canicula shows active proliferation and neurogenesis. Here, we compared the morphology and proliferative status of the retina between catshark juveniles and adults. Histological analyses revealed an important reduction in the size of the peripheral retina (where progenitor cells are mainly located), an increase in the thickness of the plexiform layers and a decrease in the thickness of the inner nuclear layer in adults. Contrary to what has been reported in teleost fish, we did not observe active mitotic activity in the catshark retina after sexual maturation, suggesting that there is no significant proliferation and neurogenesis in adult specimens. Based on these results, we carried out RNA-Sequencing (RNA-Seq) analyses comparing the retinal transcriptome of juveniles and adults, which revealed a statistically significant decrease in the expression of many genes involved in cell proliferation and neurogenesis in adult catsharks. Our RNA-Seq data provides an excellent resource to identify new signaling pathways controlling neurogenesis in the vertebrate retina.

scholarly journals Loss of Active Neurogenesis in the Adult Shark Retina

2021 ◽  
Vol 9 ◽  
Author(s):  
Ismael Hernández-Núñez ◽  
Diego Robledo ◽  
Hélène Mayeur ◽  
Sylvie Mazan ◽  
Laura Sánchez ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Plexiform Layer ◽  
Peripheral Retina ◽  
Phylogenetic Position ◽  
Postnatal Life ◽  
Inner Plexiform Layer ◽  
Rna Seq ◽  
Ancestral States ◽  
Active Proliferation ◽  
Immunohistochemical Analyses

Neurogenesis is the process by which progenitor cells generate new neurons. As development progresses neurogenesis becomes restricted to discrete neurogenic niches, where it persists during postnatal life. The retina of teleost fishes is thought to proliferate and produce new cells throughout life. Whether this capacity may be an ancestral characteristic of gnathostome vertebrates is completely unknown. Cartilaginous fishes occupy a key phylogenetic position to infer ancestral states fixed prior to the gnathostome radiation. Previous work from our group revealed that the juvenile retina of the catshark Scyliorhinus canicula, a cartilaginous fish, shows active proliferation and neurogenesis. Here, we compared the morphology and proliferative status of the retina in catshark juveniles and adults. Histological and immunohistochemical analyses revealed an important reduction in the size of the peripheral retina (where progenitor cells are mainly located), a decrease in the thickness of the inner nuclear layer (INL), an increase in the thickness of the inner plexiform layer and a decrease in the cell density in the INL and in the ganglion cell layer in adults. Contrary to what has been reported in teleost fish, mitotic activity in the catshark retina was virtually absent after sexual maturation. Based on these results, we carried out RNA-Sequencing (RNA-Seq) analyses comparing the retinal transcriptome of juveniles and adults, which revealed a statistically significant decrease in the expression of many genes involved in cell proliferation and neurogenesis in adult catsharks. Our RNA-Seq data provides an excellent resource to identify new signaling pathways controlling neurogenesis in the vertebrate retina.

scholarly journals BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuiyan Wu ◽  
You Jiang ◽  
Yi Hong ◽  
Xinran Chu ◽  
Zimu Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
Caspase 3 ◽  
Lymphoblastic Leukemia ◽  
Rna Seq ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Bet Protein

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

scholarly journals Integration of tumor inflammation, cell proliferation, and traditional biomarkers improves prediction of immunotherapy resistance and response

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarabjot Pabla ◽  
R. J. Seager ◽  
Erik Van Roey ◽  
Shuang Gao ◽  
Carrie Hoefer ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Cell Activation ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Host Immune Response ◽  
Gene Signature ◽  
B Cell Activation ◽  
Rna Seq ◽  
Multiple Tumor

Abstract Background Contemporary to the rapidly evolving landscape of cancer immunotherapy is the equally changing understanding of immune tumor microenvironments (TMEs) which is crucial to the success of these therapies. Their reliance on a robust host immune response necessitates clinical grade measurements of immune TMEs at diagnosis. In this study, we describe a stable tumor immunogenic profile describing immune TMEs in multiple tumor types with ability to predict clinical benefit from immune checkpoint inhibitors (ICIs). Methods A tumor immunogenic signature (TIGS) was derived from targeted RNA-sequencing (RNA-seq) and gene expression analysis of 1323 clinical solid tumor cases spanning 35 histologies using unsupervised analysis. TIGS correlation with ICI response and survival was assessed in a retrospective cohort of NSCLC, melanoma and RCC tumor blocks, alone and combined with TMB, PD-L1 IHC and cell proliferation biomarkers. Results Unsupervised clustering of RNA-seq profiles uncovered a 161 gene signature where T cell and B cell activation, IFNg, chemokine, cytokine and interleukin pathways are over-represented. Mean expression of these genes produced three distinct TIGS score categories: strong (n = 384/1323; 29.02%), moderate (n = 354/1323; 26.76%), and weak (n = 585/1323; 44.22%). Strong TIGS tumors presented an improved ICI response rate of 37% (30/81); with highest response rate advantage occurring in NSCLC (ORR = 36.6%; 16/44; p = 0.051). Similarly, overall survival for strong TIGS tumors trended upward (median = 25 months; p = 0.19). Integrating the TIGS score categories with neoplastic influence quantified via cell proliferation showed highly proliferative and strong TIGS tumors correlate with significantly higher ICI ORR than poorly proliferative and weak TIGS tumors [14.28%; p = 0.0006]. Importantly, we noted that strong TIGS and highly [median = not achieved; p = 0.025] or moderately [median = 16.2 months; p = 0.025] proliferative tumors had significantly better survival compared to weak TIGS, highly proliferative tumors [median = 7.03 months]. Importantly, TIGS discriminates subpopulations of potential ICI responders that were considered negative for response by TMB and PD-L1. Conclusions TIGS is a comprehensive and informative measurement of immune TME that effectively characterizes host immune response to ICIs in multiple tumors. The results indicate that when combined with PD-L1, TMB and cell proliferation, TIGS provides greater context of both immune and neoplastic influences on the TME for implementation into clinical practice.

Rapid Evaluation ofAntrodia camphorataNatural Products and Derivatives in Tumourigenic Liver Progenitor Cells with a Novel Cell Proliferation Assay

ChemMedChem ◽  
2009 ◽  
Vol 4 (10) ◽  
pp. 1657-1667 ◽  
Author(s):  
Scott G. Stewart ◽  
Louisa A. Ho ◽  
Marta E. Polomska ◽  
Alexander T. Percival ◽  
George C. T. Yeoh
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Rapid Evaluation ◽  
Proliferation Assay ◽  
Cell Proliferation Assay

scholarly journals Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

2009 ◽  
Vol 201 (1) ◽  
pp. 141-150 ◽  
Author(s):  
N David Åberg ◽  
Inger Johansson ◽  
Maria A I Åberg ◽  
Johan Lind ◽  
Ulf E Johansson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Corpus Callosum ◽  
Progenitor Cells ◽  
Parietal Cortex ◽  
Cellular Proliferation ◽  
Piriform Cortex ◽  
Adult Brain ◽  
Female Rats ◽  
Igf I

IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdU-positive cells. 3H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.

scholarly journals Progenitor cells suppress t-cell proliferation via a paracrine mechanism

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1456-P1456
Author(s):  
F. Van Den Akker ◽  
K. R. Vrijsen ◽  
J. C. Deddens ◽  
P. A. Doevendans ◽  
J. P. G. Sluijter
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Progenitor Cells ◽  
T Cell Proliferation

scholarly journals Long non-coding RNA LINC00152 regulates cell proliferation and migration by epigenetically repressing LRIG1 expression in cholangiocarcinoma

2020 ◽  
Author(s):  
Ni Wang ◽  
Yang Yu ◽  
Boming Xu ◽  
Chunmei Zhang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Function ◽  
Rna Seq ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Proliferation And Migration

Abstract Background: Recently, long non-coding RNAs (lncRNAs) have been verified to have significant regulatory roles in multiple human cancer processes. Long non-coding RNA LINC00152, located on chromosome 2p11.2, was identified as an oncogenic lncRNA in various cancers. However, the biological function and molecular mechanism of LINC00152 in cholangiocarcinoma (CCA) are still unknown.Methods: Bioinformatic analysis was performed to determine LINC00152 expression levels in the CCA and normal tissues by using raw microarray data downloaded from Gene Expression Omnibus (GSE76297) and The Cancer Genome Atlas (TCGA). Quantitative reverse transcription PCR (qRT-PCR) was used to validate LINC00152 expression in the CCA tissues compared with that in the paired normal tissues. CCK8, colony formation, Edu assays, transwell assays, flow cytometry, and in vivo tumor formation assays were performed to investigate the biological function of LINC00152 on CCA cell phenotypes. RNA-seq was carried out to identify the downstream target gene which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were performed to reveal the factors involved in the mechanism of LINC00152 functions in CCA.Results: LINC00152 is significantly upregulated in cholangiocarcinoma. LINC00152 regulated the proliferation and migration of cholangiocarcinoma cells both in vitro and in vivo. RNA-seq revealed that LINC00152 knockdown preferentially affected genes linked with cell proliferation, cell differentiation and cell adhesion. Furthermore, mechanistic investigation validated that LINC00152 could bind EZH2 and modulate the histone methylation of promoter of leucine rich repeats and immunoglobulin like domains 1 (LRIG1), thereby affecting cholangiocarcinoma cells growth and migration.Conclusion: Taken together, these results demonstrated the significant roles of LINC00152 in cholangiocarcinoma and suggested a new diagnostic and therapeutic direction of cholangiocarcinoma.

scholarly journals Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 549
Author(s):  
Niclas Björn ◽  
Ingrid Jakobsen ◽  
Kourosh Lotfi ◽  
Henrik Gréen
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Single Cell ◽  
Progenitor Cells ◽  
Myeloid Cell ◽  
Enrichment Analysis ◽  
Myelogenous Leukemia ◽  
Transcriptional Level ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Treatments that include gemcitabine and carboplatin induce dose-limiting myelosuppression. The understanding of how human bone marrow is affected on a transcriptional level leading to the development of myelosuppression is required for the implementation of personalized treatments in the future. In this study, we treated human hematopoietic stem and progenitor cells (HSPCs) harvested from a patient with chronic myelogenous leukemia (CML) with gemcitabine/carboplatin. Thereafter, scRNA-seq was performed to distinguish transcriptional effects induced by gemcitabine/carboplatin. Gene expression was calculated and evaluated among cells within and between samples compared to untreated cells. Cell cycle analysis showed that the treatments effectively decrease cell proliferation, indicated by the proportion of cells in the G2M-phase dropping from 35% in untreated cells to 14.3% in treated cells. Clustering and t-SNE showed that cells within samples and between treated and untreated samples were affected differently. Enrichment analysis of differentially expressed genes showed that the treatments influence KEGG pathways and Gene Ontologies related to myeloid cell proliferation/differentiation, immune response, cancer, and the cell cycle. The present study shows the feasibility of using scRNA-seq and chemotherapy-treated HSPCs to find genes, pathways, and biological processes affected among and between treated and untreated cells. This indicates the possible gains of using single-cell toxicity studies for personalized medicine.

scholarly journals Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qingnan Liang ◽  
Rachayata Dharmat ◽  
Leah Owen ◽  
Akbar Shakoor ◽  
Yumei Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Retinal Cell ◽  
Peripheral Retina ◽  
Marker Genes ◽  
Rna Seq ◽  
Cell Type ◽  
Retinal Tissue ◽  
The Individual

AbstractSingle-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an improved power for prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrate that obtaining single cell transcriptomes from human frozen tissues can provide insight missed by either human bulk RNA-seq or animal models.

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