HMGA2 project, CRISPR screen
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171061 | GEO | 2022/07/11
REPOSITORIES: GEO
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Project description:Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3’ untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (∆Hmga2 mice) with a 3’UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. ∆Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. ∆Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with ∆Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the ∆Hmga2+ cells. In summary, our results showed that the overexpression of a 3’UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.
2011-02-06 | GSE24071 | GEO
Project description:Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3’ untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (∆Hmga2 mice) with a 3’UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. ∆Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. ∆Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with ∆Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the ∆Hmga2+ cells. In summary, our results showed that the overexpression of a 3’UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC. Eight independent preparations of RNA, which included each 2 samples of KLS cells and MEP cells from ∆Hmga2 mice and 2 each from WT mice. Each preparation was made from 4 or 6 mice.
2011-02-06 | E-GEOD-24071 | biostudies-arrayexpress
Project description:In this study, we introduced a series of expression constructs into a mouse lung cancer cell line (482N1): (1) a control short hairpin RNA (shluc) plus the empty expression vector (empty); (2) an shRNA targeting Hmga2 (shHmga2) plus empty; (3) shHmga2 plus an expression vector for the full-length Hmga2 cDNA with the shRNA site mutated (shHmga2 wt); (4) shHmga2 plus the full-length shRNA-mutated Hmga2 with let-7 sites in the 3' UTR mutated (shHmga2 m7); (5) shHmga2 plus the full-length shRNA-mutated Hmga2 with the start codon mutated (shHmga2 ATG wt); and (6) shHmga2 plus the full-length shRNA-mutated Hmga2 with the start codon and let-7 sites mutated (shHmga2 ATG m7). Cells were plated in triplicate, RNA was prepared using RNA-Bee as per manufacturers' instructions and RNA-seq studies were performed using standard methods. For further details on library construction and next-generation sequencing, please contact the contributor.
2013-09-18 | E-GEOD-50932 | biostudies-arrayexpress
Project description:HMGA2 significantly increased cell proliferation capacity of gastric cancer in a HMGA2-dependent manner both in vivo and in vitro and we found HMGA2 promoted GC through accelerating S-G2/M phase.To elucidate the underlining mechanism by which HMGA2 induced the change of phenotype in GC cells, we performed ChIP-seq analysis of HMGA2-OE MKN-45 cells with anti-HMGA2 antibody.
2021-08-18 | GSE174442 | GEO
Project description:To provide insight into the role of and target genes of the transcription factor FOXP1 in mature human B cells and in B cell non-Hodkgin lymhomas, we performed gene expression microarray studies, upon ectopic overexpression or silencing of FOXP1 in these cells. human memory B cells from 2 separate donors were transduced with LZRS-FOXP1-IRES-YFP or LZRS-IRES-YFP (negative control); DLBCL cell lines OCI-Ly1, OCI-Ly7, and OCI-Ly10 were transduced with LZRS-FOXP1-IRES-YFP or LZRS-IRES-YFP (negative control); DLBCL cell lines OCI-Ly1, OCI-Ly7, and OCI-Ly10 were transiently transfected with siRNA targeting FOXP1 or sigenome non-targeting siRNA (negative control), using the Lonza nucleofection system.
2014-10-24 | E-GEOD-51382 | biostudies-arrayexpress
Project description:The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. Here we deciphered the role of the high mobility group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2 deficient mice (Hmga2-/-).We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2-/- mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout (KO) led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA6 (GATA binding protein 6) and FZD2 (frizzled homolog 2). Comparison of Hmga2-/- with Hmga2+/+ mice by Affymetrix microarray-based expression analysis of embryonic lung revealed an increased expression of genes whose products participate in cell cycle and canonical Wnt signaling. Affymetrix microarray transcriptome analysis of Hmga2-/- and Hmga2+/+ embryonic lung (E18.5) was performed and analyzed
2014-03-07 | E-GEOD-55340 | biostudies-arrayexpress
Project description:HMGA2 has been implicated in tumor progression. Identification of microRNAs regulated by HMGA2 helps us to understand how HMGA2 regulates tumor metastasis via its downstream target mircoRNAs and genes. Total RNA was extracted from 1833 cells with control or depleted HMGA2 expression, respectively. Exiqon miRCURY LNA 5th generation expression array was performed to identify the microRNAs regulated by HMGA2.
2014-06-01 | E-GEOD-43739 | biostudies-arrayexpress
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