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Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia

ABSTRACT: The goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis. To study this, we transduced an immortalized (but not transformed) cell line (derived from Gata1s mutant fetal liver progenitor through insertional mutagenesis) by Plag1-expressing retrovirus. This turned a non-transformed cell line to a leukemogenic cell line. To study whether Plag1 overexpression led to deregulation of signaling pathways that may contribute to leukemic transformation, we generated microarray gene expression profiles of this cell line transduced with either Plag1 or the empty vector.

ORGANISM(S): Mus musculus

PROVIDER: GSE16679 | GEO | 2010/08/01

SECONDARY ACCESSION(S): PRJNA122717

REPOSITORIES: GEO

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Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia

Project description:The goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis. To study this, we transduced an immortalized (but not transformed) cell line (derived from Gata1s mutant fetal liver progenitor through insertional mutagenesis) by Plag1-expressing retrovirus. This turned a non-transformed cell line to a leukemogenic cell line. To study whether Plag1 overexpression led to deregulation of signaling pathways that may contribute to leukemic transformation, we generated microarray gene expression profiles of this cell line transduced with either Plag1 or the empty vector. We generated gene expression profiles by microarray from stable cell lines transduced with either the empty vector or the Plag1-expressing vector.

2010-08-01 | E-GEOD-16679 | biostudies-arrayexpress

CUT&RUN of PLAG1-S global chromatin occupancy in Lin-CD34+ cord-blood cells [Cut & Run]

Project description:To characterize genome-wide chromatin occupancy of the transcription factor PLAG1-S that could contribute to transient ex vivo expansion of human cord-blood (CB) derived HSC we performed CUT&RUN. 3 pools of Lin-CD34+ CB cells transduced to overexpress 3xFLAG-PLAG1-S were used for anti-FLAG or anti-IgG control enrichment of specific PLAG1-S DNA binding sites.

2022-12-01 | GSE181975 | GEO

Developmental stage-specific interplay between GATA1 and IGF signaling in fetal hematopoiesis and leukemogenesis

Project description:This SuperSeries is composed of the following subset Series: GSE16676: Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1 GSE16677: Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples GSE16679: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia GSE16682: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors GSE16684: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling Refer to individual Series

2010-08-01 | E-GEOD-16655 | biostudies-arrayexpress

Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors

Project description:The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation.

2010-08-01 | GSE16682 | GEO

Plag1 in the mouse Epididymis

Project description:RNA sequencing of Plag1 mouse epididymides. 5 each of Plag1 WT, HET and KO whole epididymis tissues were sequenced.

2019-11-19 | GSE140576 | GEO

Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling

2010-08-01 | GSE16684 | GEO

Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors

2010-08-01 | E-GEOD-16682 | biostudies-arrayexpress

GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia

Project description:Transient leukemia (TL) is evident in 5-10% of all neonates with Down syndrome (DS) and associated with N-terminal truncating GATA1-mutations (GATA1s). Here we analyzed the effect of on gene expression upon ectopic expression of Gata1s or Gata1, while simultaneously knocking down endogenous GATA1, in wild-type CD34+-hematopoietic stem and progenitor cells during myeloid differentiation. Ectopic expression of Gata1s, but not Gata1, in wild-type CD34+-hematopoietic stem and progenitor cells induced hyperproliferation of eosinophil promyelocytes in vitro. While GATA1s retained the function of GATA1 to induce eosinophil genes by occupying their promoter regions, GATA1s was impaired in its ability to repress oncogenic MYC and the pro-proliferative E2F transcription network. We lentivirally transduced wild-type CD34+-hematopoietic stem and progenitor cells to ectopically express Gata1s or Gata1, while simultaneously knocking down endogenous GATA1, and cultured them in myeloid differentiation for 0, 4 and 14 days.

2014-03-28 | E-GEOD-56332 | biostudies-arrayexpress

PLAG1 and USF2 Co-regulate Expression of Musashi-2 in Human Hematopoietic Stem and Progenitor Cells

Project description:MSI2, which is expressed predominantly in hematopoietic stem and progenitor cells (HSPCs), enforces HSPC expansion when overexpressed and is upregulated in myeloid leukemias indicating its regulated transcription is critical to balanced self-renewal and leukemia restraint. Despite this, little is understood of the factors that enforce appropriate physiological levels of MSI2 in the blood system. Here we define a promoter region that reports on endogenous expression of MSI2 and identify USF2 and PLAG1 as transcription factors whose promoter binding drives reporter activity. We show that these factors co-regulate, and are required for, efficient transactivation of endogenous MSI2. Coincident overexpression of USF2 and PLAG1 in primitive cord blood cells enhanced MSI2 transcription and yielded cellular phenotypes, including expansion of CD34+ cells in vitro, consistent with that achieved by direct MSI2 overexpression. Global ChIP-seq analyses confirm a preferential co-binding of PLAG1 and USF2 at the promoter of MSI2, as well as regulatory regions corresponding to genes with roles in HSPC homeostasis. PLAG1 and USF2 cooperation is thus an important contributor to stem cell-specific expression of MSI2 and represents novel HSPC-specific transcriptional circuitry.

2018-03-15 | GSE111469 | GEO

Transcriptome profiling of mouse Gata1- megakaryocyte-erythroid progenitors (G1MEs) expressing one of the two isoforms of GATA1: full-length (GATA1fl) or an amino-truncated form of GATA1 (GATA1s).

Project description:We transduced mouse Gata1- megakaryocyte-erythroid progenitors with MIGRI-GFP vector expressing GATA1fl or GATA1s cDNAs. GFP-positive cells expressing one of the two isoforms of GATA1 were isolated by FACS 42 hours following transduction and used for microarray transcriptome analysis. At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. Transcriptome data for G1ME/GATA1fl at 42h were deposited previously under GSE14980 (GSM374049, GSM374050, GSM374051), whereas G1ME/GATA1s at 42h are deposited here.

2015-01-26 | GSE62879 | GEO

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