We present key transcription factors (TFs) and transcriptional regulatory networks (TRNs) delineating how they control cellular processes related to the SSC reprogramming.
Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells.
Specimen part
View SamplesType I interferons (IFN) are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDC). IRF7 is a critical regulator of type I IFN production when pathogens are detected by TLR7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. To this end, we identified the global gene expression changes after stimulation of human primary pDC with the TLR9 agonist CpGB. We identified that the transcription factor MYC is prominently upregulated upon CpGB engagement in pDC. Moreover, when we knocked down MYC in the pDC-like cell line GEN2.2, production of interferon-stimulated genes (ISGs) was dramatically increased and was further enhanced by CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with NCOR2/HDAC3 for its repression, and HDAC3 inhibition enhanced IRF7 expression and IFN production. Interestingly, activation of TLR9-mediated NF-kB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Furthermore, the inverse correlation of MYC and IRF7 was validated in psoriasis skin sample datasets. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in autoimmune diseases.
Transcriptional Repression of IFN Regulatory Factor 7 by MYC Is Critical for Type I IFN Production in Human Plasmacytoid Dendritic Cells.
Cell line
View SamplesTo address how intratumoral heterogeneity affects anti-cancer drug responses, we profiled transcriptomes of single cancer cells originating from lung adenocarcinoma patient-derived xenograft (PDX) tumors. Overall design: We performed single-cell RNA sequencing (scRNA-Seq) together with bulk sequencing by applying Smart-Seq protocol (Ramsköld et al., Nat Biotechnol 2012). Enrichment of cancer cells in PDX from primary tumor (LC-PT-45: bulk RNA-Seq, n=1) was identified by histopathological examination and genomic signatures. Tumor cell-enriched PDX cells (LC-PT-45: scRNA-Seq, n=34; bulk RNA-Seq, n=9) were analyzed, and additional batch (LC-Pt-45-Re: scRNA-Seq, n=43; bulk RNA-Seq, n=7) was obtained to check comparable results. H358 human lung cancer cells (scRNA-Seq, n=50; bulk RNA-Seq, n=1) were used as cell line controls. Another lung cancer PDX case (LC-MBT-15: scRNA-Seq, n=49; bulk RNA-Seq, n=7) was prepared to validate our analytical strategy applied in the LC-PT-45 case.
Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells.
No sample metadata fields
View Samples30 collars were taken from wild type plants or antiOsLIC transgenic plants respectively. One collar from one plant only. The leaves are just sprout 2-3 cm (about 1-2 days) from the stem. For measuring the genes expression level, Wild type plants were taken as control. The developing collar from both line2 of OsLIC antisense transgenic plants and wild type were harvested at the heading stage. The position of the collar was about 1cm above the last developed collar. Total RNA was extracted from the collars using TRIzol regeant (Invitrogen, P/N 15596-018, USA) and purified by using Qiagen RNeasy columns (QIAGEN, Cat. NO. 74104). All the processes for cDNA and cRNA synthesis, cRNA fragmentation, hybridization, washing and staining, and scanning, were conducted according to the GeneChip Standard Protocol (Eukaryotic Target Preparation, Affymetrix). Poly-A RNA Control Kit and the One-Cycle cDNA Synthesis kit were used in this experiment as described in the website: http://www.affymetrix.com/products/arrays/specific/rice.affx.
OsLIC, a Novel CCCH-Type Zinc Finger Protein with Transcription Activation, Mediates Rice Architecture via Brassinosteroids Signaling.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesFrequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable patient tumors phenocopy that represents molecular and functional heterogeneity of GBMs.
Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.
Sex, Age, Disease, Disease stage, Subject
View SamplesClear cell renal cell carcinoma (ccRCC) initiated from the renal epithelium is the most prevalent histological type of adult kidney cancers. Dissecting intratumoral heterogeneity (ITH) of ccRCC has leveraged to extend our knowledge on how primary tumors harboring driver mutations evolve and spread to other sites. The cellular fractions within and across the primary (pRCC) and metastatic RCC (mRCC) are heterogeneous in both their genetic and biological features determining the variability in clinical aggressiveness and sensitivity to the therapy. To achieve sustainable therapeutic benefit with targeted agents in mRCC, the effective target should focus on signaling pathways that are related to driver mutations occurred early in the clonal evolution of the disease and thus should be common to primary tumor and metastatic sites. Considering that extensive genetic heterogeneity may result in drug response variability among patients and treatment resistance, the tailored strategies for metastatic RCC is urgently needed. Here, we analyze single-cell RNA-seq (scRNA-seq) data from a matched primary RCC (pRCC) and lung metastasis (mRCC) to dissect ITH at the highest resolution to date with the objective of discovering the better therapeutic regimen. Overall design: In order to identify successful clonal propagation from patient to PDX samples and understand pathogenesis from primary to metastatic RCC, we performed whole-exome sequencing (WES, n=4) and matched aCGH (n=4) on bulk tumor samples. And we utilized single-cell RNA sequencing (scRNA-seq) to model and dissect functional heterogeneity acroass primary and metastatic RCC tumors. We checked whether of capturing live one cell, not more cells, in microfluidics by fluorescent microscopic observation. To construct RNA sequencing libraries, we performed further quality controls including adequate quantities and qualities of amplified transcriptomes respectively from single cells. Tumor cells from the parental mRCC (n=34), PDX-mRCC (n=36) and PDX-pRCC (n=46) were finally analyzed in this study after filtering out poor quality cells.
Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma.
No sample metadata fields
View SamplesCytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.
IL-37 protects against obesity-induced inflammation and insulin resistance.
Sex, Specimen part
View SamplesIn pluripotential reprogramming, a pluripotent state is established within somatic cells. In this study, we have generated induced pluripotent stem (iPS) cells from bi-maternal (uniparental) parthenogenetic neural stem cells (pNSCs) by transduction with four (Oct4, Klf4, Sox2, and c-Myc) or two (Oct4 and Klf4) transcription factors. The parthenogenetic iPS (piPS) cells directly reprogrammed from pNSCs were able to generate germline-competent himeras, and hierarchical clustering analysis showed that piPS cells were clustered more closer to parthenogenetic ES cells than normal female ES cells. Interestingly, piPS cells showed loss of parthenogenetic-specific imprinting patterns of donor cells. Microarray data also showed that the maternally imprinted genes, which were not expressed in pNSCs, were upregulated in piPS cells, indicating that pluripotential reprogramming lead to induce loss of imprinting as well as re-establishment of various features of pluripotent cells in parthenogenetic somatic cells.
Generation of parthenogenetic induced pluripotent stem cells from parthenogenetic neural stem cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
Specimen part
View Samples