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Biobanks of human biosamples and cell lines are indispensable for biomedical research on human health and disease and for drug development projects. Many human cell line biobanks worldwide hold collections of lymphoblastoid cell lines (LCLs), representing thousands of affected and control donors from diverse ethnic/ancestry groups. In recent years, induced human pluripotent stem cells (iPSCs) and differentiated human cells derived from these iPSCs have become indispensable for applied biomedical research. Establishing iPSCs remains a laborious and costly step towards generating differentiated human cells. To address this research need, several non‐profit and commercial biobanks have established iPSC collections for distribution to researchers, thereby serving as a resource for generating differentiated human cells. The most common starting materials for generation of iPSCs are a skin biopsy for harvesting fibroblasts, or a blood sample for collection of peripheral blood mononuclear cells. However untapped resources include the large established collections of biobanked human LCLs which can be reprogrammed to iPSCs using a variety of published protocols including the use of non‐integrating episomal vectors. Many biobanks curate LCLs from diverse ethnic/ancestry populations, an aspect largely absent in most established iPSC biobanks which tend to primarily reflect populations from developed countries. Here, we call upon researchers across the breadth of iPSC research to tap the unique resource of existing and diverse human LCL collections for establishing biobanked iPSC panels that better represent the varied human ethnic (and hence genomic) diversity, thereby benefiting precision medicine and drug development research on a global scale. [ABSTRACT FROM AUTHOR]

Biobanks are a key resource for obtaining human cell lines for biomedical research, including for drug development projects. Such projects often include comparative RNA‐sequencing of large panels of human cell lines from individuals affected by certain disorders and healthy controls, or from individuals with different drug response phenotypes. RNA extractions are typically done from growing cell cultures, a process that may take several weeks. However, maintaining large numbers of cell lines in parallel increases the project workload. Here, we show that extracting RNAs directly from frozen vials of human cell lines stored for over 20 years in a liquid nitrogen freezer yields RNAs with the high purity and integrity parameters that conform to those required for optimal RNA‐sequencing and are closely similar to those obtained for RNAs extracted from growing human cell lines. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 ( IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder. [ABSTRACT FROM AUTHOR]

Abstract: The Epstein–Barr virus encodes at least 44 microRNAs that are grouped in two clusters located around the BHRF1 gene and within the BART transcript. The expression pattern of these microRNAs both depends on the lineage of the infected cells and on the type of viral latency. Whilst BART microRNAs are expressed in all EBV-infected tumors, the BHRF1 locus is nearly exclusively expressed in cells that display a type III latency. However, the BART microRNA expression level is several orders of magnitude higher in epithelial cells than in B cells. Genetic studies have demonstrated that the BHRF1 microRNA cluster enhances the initial phases of primary B cell transformation through inhibition of apoptosis. A similar role has been ascribed to the BART microRNAs although their contribution to this process seems more limited. These microRNAs also enhance the survival of B cell lymphoma cells. Using various strategies including high throughput assays, several groups have identified mRNAs targeted by the EBV microRNAs. Here we compare the results of the published high throughput screens and review the viral and cellular genes thought to represent high confidence targets for the EBV microRNAs. Although genetic studies allow unequivocal evaluation of the functions served by the microRNAs, only a few key targets have been identified so far. [Copyright &y& Elsevier]

Highlights: [•] CNVs affecting gene expression (eCNVs) in human brain were comprehensively searched. [•] Rarer CNVs had more impact on gene expression. [•] Quarter of eCNVs located in chromosomal aberration regions causing mental disorders. [Copyright &y& Elsevier]

Abstract: Bipolar disorder (BD) is a debilitating psychiatric disease characterized by alternating episodes of mania and depression. Among mood stabilizers, lithium is the mainstay for the treatment of BD, with approximately one-third of patients showing remission from episode recurrence. While there is evidence suggesting genetic load for lithium response in BD, its molecular underpinnings are still not completely understood. To identify genes potentially involved in (or correlated with) lithium response, we carried out a genome-wide expression analysis on lymphoblastoid cell lines (LCLs) from 10 BD patients responders (R) and 10 non-responders (NR) to lithium. We compared expression levels of the two groups and tested whether in vitro lithium treatment had different effects in LCLs of R compared to NR. At basal, 2060 genes were differentially expressed between R and NR while no genes were differentially regulated by lithium in the two groups. After pathway analysis based on the 2060 genes, 9 genes were selected for validation with qRT-PCR. Eight genes were validated in the same sample of LCLs while only insulin-like growth factor 1 (IGF-1) was significantly over-expressed in R compared to NR in the same sample as well as in an independent sample comprised of 6 R and 6 NR (sample 1, fold change=1.94; p =0.005; sample 2, fold change=2.21; p =0.005). IGF-1 was also significantly over-expressed in R but not in NR when compared to a sample of non-psychiatric controls. Our findings suggest that IGF-1 may be involved in lithium response, supporting further investigation on its potential as a biomarker. [Copyright &y& Elsevier]

The aim of this work was to see whether tamarin immunisation with recombinant vaccinia virus expressing Epstein Barr Virus latent proteins could prime T cells which were, on activation, able to inhibit the outgrowth of Epstein Barr virus transformed cells in vitro. The vaccination appeared to be successful as all vaccinated tamarins developed vaccinia lesions. However, the vaccination protocol did not elicit a cell-mediated response capable of inhibiting the outgrowth of autologous Lymphoblastoid Cell Lines (LCLs) as seen in the tamarin infected with whole EBV, even though the recombinant vaccinia viruses used expressed the antigens commonly recognised by sero positive humans.

Epstein–Barr Virus-transformed B lymphoblastoid cell lines (EBV-LCLs) are routinely used for the in vitro expansion of T cells. However, these cell lines are reported to produce the cytokine IL-10, which is inhibitory for T cells. We, therefore, characterized a panel of 37 EBV-LCLs for a variety of cell surface markers, for secretion of various cytokines including IL-10 and for immunoglobulin production. These cell lines were derived from normal donors or patients with nonsmall cell lung cancer, acute myelogenous leukemia, melanoma or colon cancer. Overall, 26 lines were positive for CD19 and CD20, and 11 were negative for both. All of the lines were strongly HLA-DR+, while CD40 expression was variable. Twenty-four (65%) were both CD23+ and secreted immunoglobulin, and 33 expressed κ and/or λ light chains. Additionally, all of the EBV-LCLs were negative for T cell (CD3), NK cell (CD16, CD56), monocyte (CD14) and granulocyte (CD66b) surface markers. Some level of IL-10, IL-6, IL-12p40 and TNF-α cytokine production was detected in 33, 18, 19 and 12 EBV-LCLs, respectively. Together, these data reflect the heterogeneity of EBV-LCLs, which cautions their use nondiscriminately in various immunologic assays. [Copyright &y& Elsevier]

Determining the effect of chemotherapeutic treatment on changes in protein expression can provide important targets for overcoming resistance. Due to challenges in simultaneously measuring large numbers of proteins, a paucity of data exists on global changes. To overcome these challenges, we utilized microwestern arrays that allowed us to measure the abundance and modification state of hundreds of cell signaling and transcription factor proteins in cells following drug exposure. HapMap lymphoblastoid cell lines (LCLs) were exposed to cisplatin, a chemotherapeutic agent commonly used to treat testicular, head and neck, non-small cell lung, and gynecological cancers. We evaluated the expression of 259 proteins following 2, 6, and 12 h of cisplatin treatment in two LCLs with discordant sensitivity to cisplatin. Of these 259 proteins, 66 displayed significantly different protein expression changes (p < 0.05). Fifteen of these proteins were evaluated in a second pair of LCLs with discordant sensitivities to cisplatin; six demonstrated significant differences in expression. We then evaluated a subset of 63 proteins in a second set of LCLs with discordant sensitivity, and 40% of those that were significant in the first pair were also significant in the second part with concordant directionality (p < 0.05). We functionally validated one of the top proteins identified, PDK1, and demonstrated a synergistic relationship between cisplatin and a PDK1 inhibitor in multiple lung cancer lines. This study highlights the potential for identifying novel targets through an understanding of cellular changes in protein expression and modification following drug treatments.