The goal of this study is to investigate the molecular mechanism of lhx1 on regulation of pronephros formation during the early embryonic development. In the vertebrate embryo the kidney is derived from the intermediate mesoderm. The LIM-class homeobox transcription factor lhx1 is expressed early in the intermediate mesoderm and is one of the first genes to be expressed in the nephric mesenchyme. The animal cap cells can be induced by treatment of activin and retinoic acid to differentiate into pronephros tissue. In this study we investigated the role of Lhx1 in differentiation of pronephros by depleting lhx1 in the organ culture system. We generated the gene expression profile of early pronephros tissue, and demonstrated that expression of genes from all the kidney domains is affected by the absence of lhx1. Taken together our results highlight an essential role for Lhx1 in pronephros formation.
Lhx1 is required for specification of the renal progenitor cell field.
Specimen part, Treatment
View SamplesPTBA has been published to increase renal tubular cell proliferation, increased survival, and increased renal functional recovery in fish and various models of murine models of acute kidney injury. Immunohistological analyses suggested increased cell proliferation is accompanied by increased epithelial-to-mesenchymal transition in the RTECs. In order to elucidate pathways responsible for the increased repair response after compound treatment, larval zebrafish were given AKI and treated with PTBA analogue, UPHD25 or DMSO. Results suggests that epithelial-related genes were downregulated while mesenchymal-related genes were upregulated with injury and compound treatment. Results further validate our immunohistological finding that our compound increase post-AKI repair by increasing EMT in renal tubular cells. Overall design: At 3dpf, larval zebrafish are given acute kidney injury with gentamicin microinjection. 2 days post injury, larvae with AKI are selected and treated with 1uM of PTBA analogue, UPHD25 or vehicle control, 1% DMSO. The fish were treated with UPHD25 or DMSO for 24 hours. Then, pronephric kidneys were collected using DDT, collagenase I, and manual collection. Total 100 larvae were collected per sample, per replicate. Each treatment group was repeated with 3 biological replicates. RNA was collected and sequenced.
Enhancing regeneration after acute kidney injury by promoting cellular dedifferentiation in zebrafish.
Specimen part, Treatment, Subject
View SamplesRenal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated.
Histone deacetylase inhibitor enhances recovery after AKI.
Specimen part
View SamplesThe effect of prototypical pregnane receptor X (PXR) agonist (pregnenolone 16-carbonitrile) PCN on hepatic gene expression was studied in mice primary hepatocytes.
Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver.
Sex, Treatment
View SamplesComparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis.
The cytotoxic T cell proteome and its shaping by the kinase mTOR.
Specimen part, Treatment
View SamplesThe PARK2 gene was knocked down using 2 independent siRNAs in SNB19 and SF539 cell lines
Pan-cancer genetic analysis identifies PARK2 as a master regulator of G1/S cyclins.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View Samples