Project description:To study the transcriptional profiling of seedling roots under different solution pH stresses in winter wheat (Triticum aestivum L.). We identify genes that are differentially expressed in response to different solution pH (4.0 and 10.0) comparing with control pH 6.5 using microarray technology.
Project description:Cell-type specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) sorting of roots that express cell-type specific GFP-reporters. Five different GFP-reporter lines were used. FACS cell populations were isolated from roots grown under standard pH (pH 5.7) or roots that had been transfered to low pH (pH 4.6) media for 24 hours. Stress responses in plants are tightly coordinated with developmental processes, but the interaction between these pathways is poorly understood. Here we use genome-wide assays at high spatial and temporal resolution to understand the processes that lnk development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. Common stress responses appear to exists and, analagous to animal systems, many of them show cell-type specificity, suggesting a convergent evolutionary theme in multicellular organisms. Common stress responses may be mediated by cell identity regulators, as mutations in these genes resulted in altered responses to stress. Our results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide datasets to elucidate biological processes.
Project description:We aim to compare the genomic discrepancies across de novo Ph+ ALL, Ph+ MPAL and Ph+ AML, three diseases characterized by the occurrence of BCR-ABL1 transcripts but showing varied immunophenotypes. The data we are now submitting is the genomic copy number variants of these three groups. The following is the abstract with associated manuscript. The chromosome abnormality of Philadelphia (Ph) is typically seen in de novo acute lymphoblastic leukemia (ALL). It has also been identified in mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) in the revisions to World Health Organization classification of myeloid neoplasms and actue leukemia. The discrepancies between these patients and potential mechanisms underlying differentiation fate of the leukemia cells remain poorly defined. We evaluated the clinical, genomic and transcriptomic features of Ph+ ALL, Ph+ MPAL and Ph+ AML by taking advantage of high-density genomic analysis, including next-generation sequencing array comparative genomic hybridization and gene expression profiling for transcriptomic analysis. Our results showed that the three cohorts demonstrated diversified clinical features. Ph+ ALL had the best response to induction therapy, with a complete remission (CR) rate of 93.5 and molecular response of 43.5%. Ph+ MPAL had a 90.0% CR rate but only 5.9% of molecular response. The CR rate of Ph+ AML was only 68.8%. Ph+ ALL was characterized by loss and mutations of B-cell development gene IKZF1 and PAX5, and frequent histone H3K36 trimethyltransferase SETD2 mutations. SETD2 mutations were detected in 11.3% of Ph+ ALL patients and predicted higher relapse rate. Ph+ MPAL and Ph+ AML featured high frequency of RUNX1 mutations. Further studies showed RUNX1-R177X mutation inhibited 32D cell differentiation induced by G-Csf, and cooperated with BCR-ABL1 to lead to myeloid differentiation arrest of human cord blood CD34+ cells. It is therefore presumed that these additional mutations work in synergy with BCR-ABL1 fusion gene to facilitate the development of Ph-positive acute leukemia in different immunophenotypic classifications.
Project description:Cell-type specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) sorting of roots that express cell-type specific GFP-reporters. Five different GFP-reporter lines were used. FACS cell populations were isolated from roots grown under standard pH (pH 5.7) or roots that had been transfered to low pH (pH 4.6) media for 24 hours. Stress responses in plants are tightly coordinated with developmental processes, but the interaction between these pathways is poorly understood. Here we use genome-wide assays at high spatial and temporal resolution to understand the processes that lnk development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. Common stress responses appear to exists and, analagous to animal systems, many of them show cell-type specificity, suggesting a convergent evolutionary theme in multicellular organisms. Common stress responses may be mediated by cell identity regulators, as mutations in these genes resulted in altered responses to stress. Our results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide datasets to elucidate biological processes. 3 replicates for each of 5 cell types for low pH and standard pH (30 samples total).
Project description:The paper describes a model of pH control in tumor.
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This model is described in the article:
Regulation of tumour intracellular pH: A mathematical model examining the interplay between H and lactate
Maymona Al-Husari, Steven D. Webb
Journal of Theoretical Biology 322 (2013) 58–71
Abstract:
Non-invasive measurements of pH have shown that both tumour and normal cells have intracellular pH (pHi) that lies on the alkaline side of neutrality (7.1–7.2). However, extracellular pH (pHe) is reported to be more acidic in some tumours compared to normal tissues. Many cellular processes and therapeutic agents are known to be tightly pH dependent which makes the study of intracellular pH regulation of paramount importance. We develop a mathematical model that examines the role of various membrane-based ion transporters in tumour pH regulation, in particular, with a focus on the interplay between lactate and H ions and whether the lactate/H symporter activity is sufficient to give rise to the observed reversed pH gradient that is seen is some tumours. Using linear stability analysis and H ions. We extend this analysis using perturbation techniques to specifically examine a rapid change in H-ion concentrations relative to variations in lactate. We then perform a parameter sensitivity analysis to explore solution robustness to parameter variations. An important result from our study is that a reversed pH gradient is possible in our system but for unrealistic parameter estimates—pointing to the possible involvement of other mechanisms in cellular pH gradient reversal, for example acidic vesicles, lysosomes, golgi and endosomes.
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