Identification of a LIF-responsive replication-competent human β cell
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA573954 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10180914.fastq.gz | Fastqsanger.gz | |||
| SRR10180915.fastq.gz | Fastqsanger.gz | |||
| SRR10180916.fastq.gz | Fastqsanger.gz | |||
| SRR10180917.fastq.gz | Fastqsanger.gz | |||
| SRR10180918.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 22 |
Similar Datasets
Project description:The beta (β) cell mass formed during embryogenesis is amplified by cell replication that occurs primarily during fetal and early postnatal development. Thereafter, β cells become functionally mature and their mass is maintained by a very low rate of replication. For those few β cells that replicate in adult life, it is not known how replication is initiated, uncoupled from β cell function nor whether this occurs in a specialized subset of β cells. To explore these issues with the aim of controlling replication of mature human β cells, we capitalized on a YAP overexpression system that induces cell cycle re-entry in stem cell derived-β cells. Singe cell RNA sequencing revealed an upregulation of components of the leukemia inhibitory factor (LIF) pathway upon cell cycle re-entry. Experimental activation of the LIF pathway induces replication and expansion of human stem cell derived- and adult β cells in vitro and in vivo. In both stem cell derived- and adult human β cells, the expression of the LIF receptor LIFR is restricted to a subset of β cells with distinct transcriptional profiles and defines a subpopulation of β cells with increased replication rates. Further analysis identified 15 transcription factors whose gene networks are active in replicating β cells. Overall, this study sheds light on regulatory networks that control β cell replication and reveals a heterogeneity in LIF responsiveness and replication competence.
2019-09-25 | GSE137961 | GEO
Project description:LIF has an important role in immunosupression in different scenarios, such as in embryo implantation in the uterus, autoimmune disease or organ transplantation. In tumor progression it has been largely demonstrated the importance of immune system. The fact that LIF is highly expressed in certain tumor types, in addition to its immunomodulatory properties, led us to hypothesize that tumors expressing high levels of LIF might be promoting an immune-tolerant microenvironment precluding the anti-tumor immune response. To establish whether the effect of LIF was relevant in the context of human monocytes, we isolated CD14+ cells (monocytes) from peripheral blood mononuclear cells (PBMCs) from healthy donors and analyzed the effect of LIF blockade. Instead of using recombinant LIF, we studied the effect of the endogenous LIF secreted by U251 cell line. RNA was extracted from the CD14+ cells and the transcriptomic analysis was performed.
2022-02-01 | GSE79851 | GEO
Project description:The comprehensive characterization and quantification of the HIV tissue reservoirs is required to design appropriate therapeutic intervention(s) to achieve a cure. While pioneering studies demonstrated that HIV replication and spreading mainly occur in lymphoid tissues, the identification of specific cell subsets harboring replication competent virus in lymphoid tissues has long been neglected. In this context, we and others have recently shown that gut memory CD4 T cells, lymph node T follicular helper (Tfh) cells and tissue macrophages represent major HIV/SIV tissue reservoirs. Notably, Tfh cell differentiation is a multi-stage process that requires long-lasting interactions with lymph node (LN) dendritic cells (DCs) and pre-germinal center B cells in a specific cytokine/chemokine microenvironment. Lymph node DCs are endowed with an exceptional T-cell stimulatory potential and can either migrate from the periphery to the draining lymph node (migratory DCs) or locate in the LN for their entire life span (resident DCs). On the basis of these unique properties, long-term persistence of LN DCs infected with replication competent virus may represent the initial trigger of viral rebound post ART interruption and may therefore represent a major obstacle to HIV cure. We demonstrate that LN migratory DCs are infected with replication competent virus and persist despite suppressive ART. In addition, we identified the mechanisms associated with i) LN DC susceptibility to HIV infection and ii) long term persistence of HIV-infected LN DCs i.e. proliferation of infected cells in tissue sanctuaries.
2023-09-13 | GSE196066 | GEO
Project description:Leukemia inhibitory factor (LIF) is an important endogenous factor for photoreceptor protection. Lif is known to be upregulated both in induced and inherited disease models of photoreceptor degeneration only in a subset of Muller cells. Since Lif is induced in Muller cells in response to photoreceptor injury, we studied its regulation in Muller cells. We have recently identified several AU-rich elements (AREs) within the 3′ untranslated region (UTR) of Lif . We also showed that as a result of these elements Lif encodes a highly unstable mRNA. mRNAs containing AREs in the 3`UTR undergo rapid ARE-mediated mRNA decay in the cytoplasm which is mediated by the RNA–binding proteins. In order to identify the RNA-binding proteins that are involved in the regulation of Lif transcripts, we will use the biotin-labelled RNA. By using this methodology, we will isolate the related RNA binding proteins. We plan to analyze the isolated proteins by mass spectrometry, and compare the mass spectrometry results of different regions with or without AREs . Once we identify the specific proteins that bind only to AREs, we will do the functional characterization of these proteins by cotransfecting the constructs with AREs and the siRNA that inhibits the expression of related RNA binding protein.
2016-07-20 | PXD001463 | Pride
Project description:Separation of DNA replication from the assembly of break-competent meiotic chromosomes
| PRJNA152437 | ENA
Project description:LIF has an important role in immunosupression in different scenarios, such as embryo implantation in the uterus, autoimmune disease or organ transplantation. We decided to study the role of LIF on the immune response to cancer. We found that tumors expressing high levels of LIF promote an immune-tolerant microenvironment precluding the anti-tumor immune response. To establish the effect of LIF on tumor-associated myeloid cells (TAMCs), we used a syngeneic ovarian tumor model (ID8 cell line). We treated animals bearing tumors with anti-LIF antibody and isolated myeloid (CD11b+) cells from the ascites. RNA was extracted from the CD11b+ cells and the transcriptomic analysis was performed.
2019-04-23 | GSE79852 | GEO
Project description:Leukemia Inhibitory Factor (LIF) plays an essential role in the maintenance of pluripotency of mouse embryonic stem cells (mESCs). LIF withdrawal induces mESC differentiation. To define noval pluripotent factors downstream of LIF signaling, cDNA microarray was used and seveal well-known pluripotent genes were found to respond to LIF withdrawal, including Klf4, Esrrb, Tbx3, and Prdm14.
2015-06-23 | GSE70104 | GEO
Project description:Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART
| PRJNA803203 | ENA
Project description:Replication-competent HIV-1 gRNA Constructs for CRISPR/Cas9-based Discovery of Antiviral Factors
| PRJNA1028668 | ENA
Project description:Innate cellular defense mechanisms and viral countermeasures govern the outcome of pathogen exposure but the complex virus-host interplay remains poorly understood. Here, we developed a virus-guided technology platform where the pathogen itself reveals its cellular opponents. To accomplish this, we engineered replication-competent HIV-1 expressing single guide RNAs (sgRNAs) targeting potential antiviral genes in Cas9 expressing CD4+ T cells. Screening of HIV-1 constructs targeting >500 potential antiviral genes revealed that sgRNAs against GRN, CIITA, EHMT2, CEACAM3, CC2D1B, RHOA and HMOX1 provide significant advantages for viral replication. We verified that GRN and CIITA inhibit HIV-1 in primary CD4+ T cells by reducing viral transcription. Lack of the accessory nef gene increased selection for sgRNAs targeting SERINC5 and IFI16. Functional analyses demonstrated that Nef counteracts the inhibitory effects of IFI16. Altogether, we established a highly versatile, effective and robust approach that forces HIV-1 to reveal its cellular opponents.
2024-04-15 | GSE245526 | GEO