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Project description:Effect of pH modulation on cardiomyocyte differentiation
| PRJNA869458 | ENA
Project description:The purpose of this study was to understand how prevention of serine/threonine protein kinase (STPK) phosphorylation of PrrA impacts PrrA modulation of M. tuberculosis transcriptional response to acidic pH and high chloride levels.
2022-06-23 | GSE199000 | GEO
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.
2022-04-29 | GSE130484 | GEO
Project description:The mechanistic target of rapamycin complex 2 (mTORC2) is essential for embryonic development but the underlying molecular mechanisms remain unclear. Here we show that disruption of mTORC2 in human embryonic stem cells (hESCs) considerably alters the balance of Rho/Rac signaling and reduces cell adhesion. Although these changes have no clear effect on their self-renewal and the expression of pluripotent markers, they significantly impede BMP-induced activation of canonical WNT genes, leading to impaired mesendoderm differentiation. Direct activation of the downstream WNT pathway by inhibiting GSK3 dramatically improves mesendoderm differentiation in mTORC2-deficient hESCs. Our studies uncover a new mechanism by which mTORC2 regulates cell fate determination and link the intercellular contacts with the activation of WNT genes.
2023-11-06 | GSE243723 | GEO
Project description:Metals at high concentrations can exert toxic effects on microorganisms. It has been widely reported that lowering environmental pH reduces effects of cadmium toxicity in bacteria. Understanding the effects of pH-mediated cadmium toxicity on bacteria would be useful for minimizing cadmium toxicity in the environment and gaining insight into the interactions between organic and inorganic components of life. Growth curve analysis confirmed that cadmium was less toxic to Escherichia coli at pH 5 than at pH 7 in M9 minimal salts medium. To better understand the cellular mechanisms by which lowering pH decreases cadmium toxicity, we used DNA microarrays to characterize global gene expression patterns in E. coli in response to cadmium exposure at moderately acidic (5) and neutral (7) values of pH. Higher expression of several stress response genes including hdeA, otsA, and yjbJ at pH 5 after only 5 minutes was observed and may suggest that acidic pH more rapidly induces genes that confer cadmium resistance. Genes involved in transport were more highly expressed at pH 7 than at pH 5 in the presence of cadmium. Of the genes that showed an interaction between pH and cadmium effects, 46% encoded hypothetical proteins, which may have novel functions involved in mitigating cadmium toxicity.
2008-08-21 | GSE12373 | GEO
Project description:Immune Modulation in Psoriasis Lesions by Topical PH-10 (Rose Bengal Disodium)
| PRJNA636809 | ENA
Project description:TGF-β signaling is a central regulator of early development in metazoans, yet our understanding of the scope of TGF-β signaling’s downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we found that a highly conserved, primitive-streak-specific micropeptide is a direct target of TGF-b/Nodal signaling. This transmembrane micropeptide (NEMEP) is essential for mesendoderm differentiation. Depletion of NEMEP impaired mesendoderm differentiation and caused a significant decrease in glucose uptake, while TGF-β signaling enhances glucose uptake in a NEMEP-dependent manner. Biochemically, we show that NEMEP promotes glucose uptake through its interactions with GLUT1/3. Thus, beyond expanding the scope of known TGF-β signaling targets in early development and showing that this target micropeptide augments the glucose uptake function of major glucose transporters during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered metabolism on cell fate determination in early embryogenesis.
2021-11-03 | GSE157073 | GEO
Project description:Copy number variations of Ph+ ALL, Ph+ MPAL and Ph+ AML
| PRJNA540459 | ENA
Project description:Purpose: Here we describe the modulation of a gene expression program involved in cell fate. Methods: We depleted U2AF1 in human induced pluripotent stem cells (hiPSCs) to the level found in differentiated cells using an inducible shRNA system, followed by high-throughput RNAseq, revealing a gene expression program involved in cell fate determination. Results: Approximately 85% of the total raw reads were mapped to the human genome sequence (GRCh37), giving an average of 200 million human reads per sample for total RNA and 15 million human reads per sample for small RNA libraries. Conclusions: Our results show that transcriptional control of gene expression in hiPSCs can be set by the CSF U2AF1, establishing a direct link between transcription and AS during cell fate determination.
2018-12-03 | GSE119700 | GEO