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A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells

ABSTRACT: Human cord blood CD34+ cells transduced with control of IK6 lentivirus were transplanted into NSG mice. Control and IK6 transduced CD34+38- progeny were acquired 10 weeks later by FACS

ORGANISM(S): Homo sapiens

PROVIDER: GSE60957 | GEO | 2014/09/14

SECONDARY ACCESSION(S): PRJNA259963

REPOSITORIES: GEO

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A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells

Project description:Human cord blood CD34+ cells transduced with control of IK6 lentivirus were transplanted into NSG mice. Control and IK6 transduced CD34+38- progeny were acquired 10 weeks later by FACS Comparison of control and IK6+ human CD34+38- progenitor cells

2014-09-14 | E-GEOD-60957 | biostudies-arrayexpress

A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells.

Project description:Disrupted IKAROS activity is a recurrent feature of some human leukemias, but effects on normal human hematopoietic cells are largely unknown. Here, we used lentivirally mediated expression of a dominant-negative isoform of IKAROS (IK6) to block normal IKAROS activity in primitive human cord blood cells and their progeny. This produced a marked (10-fold) increase in serially transplantable multipotent IK6(+) cells as well as increased outputs of normally differentiating B cells and granulocytes in transplanted immunodeficient mice, without producing leukemia. Accompanying T/natural killer (NK) cell outputs were unaltered, and erythroid and platelet production was reduced. Mechanistically, IK6 specifically increased human granulopoietic progenitor sensitivity to two growth factors and activated CREB and its targets (c-FOS and Cyclin B1). In more primitive human cells, IK6 prematurely initiated a B cell transcriptional program without affecting the hematopoietic stem cell-associated gene expression profile. Some of these effects were species specific, thus identifying novel roles of IKAROS in regulating normal human hematopoietic cells.

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BCR-ABL1 and a dominant negative isoform of Ikaros cooperate to induce human acute myeloid leukemia

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BCR-ABL1 and a dominant negative isoform of Ikaros cooperate to induce human acute myeloid leukemia

Project description:Analysis of lineage depleted human cord blood cells sequentially transduced with retro- (BCR-ABL1) and lentiviral (Ik6) vectors and the corresponding controls. Results provide important informations on the collaboration of BCR-ABL1 and Ik6 in human hematopoietic cells. Double-transduced lineage depleted human cord blood cells were puirifed according to GFP and LNGFR expression. RNA was extracted from purified cells.

2014-05-23 | E-GEOD-45452 | biostudies-arrayexpress

bulkRNA seq of spleens from humanized mice comparing NRG to NSG-DKO strains and additionally vaccination using lentiviral constructs

Project description:Decifering why NSG-DKO mice have better humanization upon CD34+ stem cell injection than NRG mice. Additionally, checking effects of lentivirus administration that delivers human HLAs, human cytokines and a viral antigen, which, as a consequence, should improve human adaptive immunity in our huNSG-DKO mouse model.

2024-04-01 | E-MTAB-13883 | biostudies-arrayexpress

BRAFV600E or mutant MAP2K1 human CD34+ cells establish Langerhans cell-like histiocytosis in immunodeficient mice

Project description:We describe a xenograft model for human LCH-like disease in which we transduced human Cord Blood CD34+ HSPCs with a virus coding for BRAF-V600E - the most abundant pathognomonic somatic mutation occuiring in LCH. Cells were subsequently subjected to RNA-sequencing or transplanted into humanized MISTRG or NSG mice.

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Transcriptomic analysis of the in vivo effects of CDK8/19 inactivation in 22Rv1 xenografts growing in intact and castrated NSG mice

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2024-03-31 | GSE240370 | GEO

Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL [ATAC-Seq]

Project description:Using patient-derived Ph+ pre-B ALL cells that harbor deletions of the IKZF1 DNA binding domain (Ik6), we performed ATAC-sequencing in cells that inducibly express wild-type Ikaros (Ik1) or an empty vector control.

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Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL [ChIP-seq]

Project description:ChIP-seq was performed in patient-derived BCR-ABL1+ (Ph+) pre-B ALL cells that harbor heterozygote deletions of the IKZF1 DNA binding domain (Ik6), using cells that inducibly express wild-type Ikaros (Ik1) or an empty vector control.

2017-02-06 | GSE90656 | GEO

The gene expression upon dominant negative form of GAS2 (GAS2DN) in MEG-01 cells

Project description:GAS2DN could suppress the growth of chronic myeloid leukemia cells, including K562, MEG-01 and CD34+ cells from patients. In addition, GAS2DN inhibited the tumorigenic ability of MEG-01 cells in nude mice. To understand the molecular insight of this inhibitory effect of GAS2DN, global gene expression were performed. The control and GAS2DN-transduced MEG-01 cells were used for microarray analysis.

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