Treatment of severely refractory Crohn's disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT. Overall design: Biopsy mRNA profiles of 14 CD patients undergoing HSCT were generated by deep sequencing, using HiSeq-4000 platform (Illumina, San Diego, CA).
Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.
Sex, Specimen part, Disease, Subject
View SamplesThe transcriptional signature of mucosa of patients with ulcerative colitis (UC) in remission reveals long-lasting changes in the epithelial barrier which persist once the inflammatory response has resolved. In order to investigate if these changes are caused by primary defects in the epithelial cells, we generated in vitro epithelial organoid cultures (EpOCs) from colon samples of non-IBD controls and UC patients.
Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis.
Age, Specimen part
View SamplesTranscriptional profile of control and VEGF overexpressing FACS-isolated CD34+ Cancer stem cells from DMBA/TPA induced skin tumours
A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours.
No sample metadata fields
View SamplesDifferentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect the mechanisms controlling intratumoral heterogeneity within basal-like breast cancers. We show that cancer cells can transition between a differentiation state related to that of normal luminal progenitors and a state closer to that of mature luminal cells, and that this occurs through asymmetric cell divisions. The Polycomb factor EZH2 and the Notch pathway act to increase the rates of symmetric divisions that produce progenitor-like cells, while the FOXA1 transcription factor promotes asymmetric divisions that reduce the numbers of such cells. Through functional screening, we identified a group of regulators that control cancer cell differentiation state and the relative proportions of tumor cell subpopulations. Our findings highlight the regulation of asymmetric cell divisions as a mechanism controlling intratumoral heterogeneity, and identify molecular pathways that control breast cancer cellular composition. Overall design: Expression profiles of HCC70 cells expressing shRNAs targeting regulatory factors that influence basal-like cancer cell population composition
Regulation of Cellular Heterogeneity and Rates of Symmetric and Asymmetric Divisions in Triple-Negative Breast Cancer.
Cell line, Subject
View SamplesDifferentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect the mechanisms controlling intratumoral heterogeneity within basal-like breast cancers. We show that cancer cells can transition between a differentiation state related to that of normal luminal progenitors and a state closer to that of mature luminal cells, and that this occurs through asymmetric cell divisions. The Polycomb factor EZH2 and the Notch pathway act to increase the rates of symmetric divisions that produce progenitor-like cells, while the FOXA1 transcription factor promotes asymmetric divisions that reduce the numbers of such cells. Through functional screening, we identified a group of regulators that control cancer cell differentiation state and the relative proportions of tumor cell subpopulations. Our findings highlight the regulation of asymmetric cell divisions as a mechanism controlling intratumoral heterogeneity, and identify molecular pathways that control breast cancer cellular composition. Overall design: Expression profiles of three cell subpopulations – K18+, K18+K14+ and K18+Vim+ – sorted from the breast cancer cell lines HCC70 and MDA-MB-468
Regulation of Cellular Heterogeneity and Rates of Symmetric and Asymmetric Divisions in Triple-Negative Breast Cancer.
Cell line, Subject
View SamplesNatural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs.
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Sex, Specimen part
View SamplesFinding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients.
The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.
Sex, Age, Specimen part, Race
View SamplesTranscriptional Profiling Reveals Distinguishing Features of Immune Activation in the Lymphatic Tissues of Sooty Mangabeys and Rhesus Macaques in Early SIV Infection
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Specimen part
View SamplesWe profiled the transcriptome of matched diagnosis and relapse samples from 10 pediatric B precursor Acute Lymphoblastic Leukemia (ALL) patients using massively parallel sequencing (RNA-Seq) technology to identify novel mutations specific at disease recurrence.
Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.
No sample metadata fields
View SamplesDirect cell reprogramming has enabled the direct conversion of skin fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell lineage-specific transcription factors. This approach has substantial advantages since it is rapid and simple, generating the cell type of interest in a single step. However, it remains unknown whether this technology can be applied for directly reprogramming skin cells into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB and SOX9 to be sufficient to convert with high efficiency embryonic and post-natal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications.
Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.
Specimen part
View Samples