scholarly journals Temperature-sensitive v-sea transformed erythroblasts: a model system to study gene expression during erythroid differentiation.

1988 ◽  
Vol 2 (2) ◽  
pp. 247-258 ◽  
Author(s):  
J Knight ◽  
M Zenke ◽  
C Disela ◽  
E Kowenz ◽  
P Vogt ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3524-3524
Author(s):  
Anil Potti ◽  
Holly K. Dressman ◽  
Murat O. Arcasoy

Abstract Hematopoietic proliferation, lineage commitment, and terminal differentiation are characterized by the emergence of a cell type-specific gene expression and transcriptional programs that determine the specific phenotype and function of cells in the erythroid lineage. Our objectives in this study were to identify unique gene expression patterns that characterize the transcriptional program of normal primary human erythroid precursors during terminal differentiation, and define the gene expression patterns seen in erythroblasts (EBL) of patients with polycythemia vera (PV). Homogenous populations of primary proEBL were generated from purified liquid cultures of CD34+ cells collected from healthy volunteers and PV patients. All patients with PV were diagnosed based on established criteria and had the JAK2-V617F mutation. Morphologic examination and surface expression of CD71 confirmed the purity of proEBL cell populations. ProEBL from normal individuals were induced to terminally differentiate generating orthochromatic EBL. RNA was extracted from normal proEBL, PV proEBL, and normal orthochromatic EBL. Affymetrix U133 Plus 2.0 arrays representing approximately 39,000 human genes were used for gene expression analysis. Four replicates from four independent primary cell cultures were analyzed for each comparison group (e.g. undifferentiated proEBL versus terminally differentiated orthochromatic EBL). Unsupervised hierarchical clustering showed distinct gene expression profiles in the proEBL and terminally differentiated EBL lineages. 1109 genes (2.0 fold change, P<0.01) were found to be differentially expressed. Numerous erythroid genes were found to be upregulated during terminal differentiation [e.g. globin genes, erythropoietin receptor, heme synthesis enzymes (ferrochelatase, ALAS2) erythrocyte membrane proteins (band 3, ankyrin, protein 4.1) and transcription factors (NFE2, Kruppel-like factors, myb, GATA2)]. As a proof of validation, the differential expression of 7 genes was verified by Northern blotting. To better understand the biologic role of the gene sets identified, using Ingenuity pathway analysis, individual genes were integrated into specific regulatory and signaling pathway networks. A total of 19 networks with significant scores (>23) were identified. Biological functions of the identified networks included RNA post-transcriptional regulation, cell cycle control, translational regulation, DNA replication and repair and cellular assembly/organization. In a proof of principle study, gene expression patterns in PV proEBL (n=6) were compared to normal proEBL (n=5). Unsupervised hierarchical clustering showed a distinct gene expression profile for PV. A binary regression predictive model was also developed to find gene expression patterns predictive for PV. Using this model a 150 gene predictor was found that could predict PV patients from control at 100% accuracy. Ingenuity pathways analysis of a subset of gene subsets demonstrated several biologically relevant networks that were distinct in patients with PV, including myc, CDC2, and JAK2. Deregulation of normal transcriptional mechanisms in hematopoietic cells is associated with the pathogenesis of PV. Further, our data shows that genomic studies provide new insights into transcriptional programs that govern erythroid differentiation, and identify biologically relevant deregulated pathways as potential targets for therapy in PV.



Zuriat ◽  
2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Nono Carsono ◽  
Christian Bachem

Tuberization in potato is a complex developmental process resulting in the differentiation of stolon into the storage organ, tuber. During tuberization, change in gene expression has been known to occur. To study gene expression during tuberization over the time, in vitro tuberization system provides a suitable tool, due to its synchronous in tuber formation. An early six days axillary bud growing on tuber induction medium is a crucial development since a large number of genes change in their expression patterns during this period. In order to identify, isolate and sequencing the genes which displaying differential pattern between tuberizing and non-tuberizing potato explants during six days in vitro tuberization, cDNA-AFLP fingerprint, method for the visualization of gene expression using cDNA as template which is amplified to generate an RNA-fingerprinting, was used in this experiment. Seventeen primer combinations were chosen based on their expression profile from cDNA-AFLP fingerprint. Forty five TDFs (transcript derived fragment), which displayed differential expressions, were obtained. Tuberizing explants had much more TDFs, which developmentally regulated, than those from non tuberizing explants. Seven TDFs were isolated, cloned and then sequenced. One TDF did not find similarity in the current databases. The nucleotide sequence of TDF F showed best similarity to invertase ezymes from the databases. The homology of six TDFs with known sequences is discussed in this paper.



2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Fatma Demet Arslan ◽  
Ayse Kocak ◽  
Cengiz Aydın ◽  
Emel Ebru Pala ◽  
Dilek Oncel ◽  
...  

AbstractObjectivesThe recurrence of rectal cancer or its resistance to neoadjuvant treatment develops due to the adaptation to hypoxia, apoptosis or autophagy. Survivin, one of the inhibitors of apoptosis; Beclin 1, which is a positive regulator in the autophagy pathway; and hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA9), which are associated with tumor tissue hypoxia, may be related to resistance to treatment. Our aim was to evaluate the potential tumor markers that may help to monitor the response to neoadjuvant treatment in locally advanced rectal cancer (RC).MethodsTwenty-five patients with locally advanced RC were included in the study. Gene expression and protein levels of Beclin 1, Survivin, HIF-1α, and CA9 were analyzed in fresh tissue specimens and blood samples. The relationships of these markers to tumor staging and regression grade were evaluated.ResultsHigher blood CA9 gene expression levels and lower blood HIF-1α protein levels were found in the response group according to tumor regression grade. After neoadjuvant treatment, tissue Beclin 1 and blood Survivin gene expressions and tissue CA9, blood Beclin 1 and blood HIF-1α protein levels decreased significantly.ConclusionBeclin 1, Survivin, HIF-1α ve CA9 may help to predict the effects of the applied treatment approach.



2013 ◽  
Vol 304 (3) ◽  
pp. R177-R188 ◽  
Author(s):  
Wendi S. Neckameyer ◽  
Kathryn J. Argue

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.



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