GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE62853 Query DataSets for GSE62853
Status Public on Nov 28, 2023
Title Modeling myelodysplastic syndromes in mice by altered Hoxa1 spliceform expression
Organism Mus musculus
Experiment type Expression profiling by array
Summary The homeobox gene, Hoxa1, has two different isoforms generated by alternative splicing: a full-length homeodomain-containing Hoxa1 (Hoxa1-FL), and a truncated Hoxa1 (Hoxa1-T), that lacks the homeodomain. Oncoretroviral overexpression of wildtype Hoxa1 cDNA (WT-Hoxa1), which generates both Hoxa1 isoforms, in murine hematopoietic stem and progenitor cells (HSPCs) perturbed hematopoiesis, resulting in myelodysplastic syndromes (MDS) in mice. Overexpression of a mutated Hoxa1 cDNA (MUT-Hoxa1) that generates Hoxa1-FL but not Hoxa1-T led to a more severe MDS capable of transforming to secondary acute myeloid leukemia (sAML). Similar to human MDS, DNA damage repair pathways were downregulated in Hoxa1-overexpressing hematopoietic progenitor cells. Conditional knock-in mouse models revealed a Hoxa1-FL dosage-dependent effect on MDS disease severity. Our data reveal that increased expression of Hoxa1-FL in HSPCs is sufficient to initiate MDS in mice. CD34+ cells from up to 50% of patients with MDS had elevated HOXA1-FL expression, highlighting the clinical relevance of our mouse models.
Overall design 5000-78,000 sorted (MEP) cells with overexpression of Wild type Hoxa1 (WT- Hoxa1), Mutant Hoxa1 (MUT-Hoxa1) or control vector (MXIE) from primary recipient mice 16 weeks post transplantation.
Three vector groups (MXIE, WT-Hoxa1 and MUT-Hoxa1) were compared.
Joseph C: St. Vincent’s Institute, Melbourne, Australia
Hendy J: St. Vincent’s Institute, Melbourne, Australia
Baker EK: St. Vincent’s Institute, Melbourne, Australia
Chalk AM: Stem Cell Regulation Unit, St. Vincent’s Institute, Melbourne, Australia
Gudas LJ: Department of Pharmacology, Weill Cornell Medical College, New York, NY
Fabb SA: Monash University, Carlton, Australia
Wall M: Victorian Cancer Cytogenetics Service, St. Vincent’s Hospital, Melbourne, Australia
Walkley CR: St. Vincent’s Institute, Melbourne, Australia
Purton LE: St. Vincent’s Institute, Melbourne, Australia
Web link
Contributor(s) Joseph C, Hendy J, Baker EK, Chalk AM, Gudas LJ, Fabb SA, Wall M, Walkley CR, Purton LE
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Oct 30, 2014
Last update date Nov 29, 2023
Contact name Alistair Morgan Chalk
Organization name St Vincent's Institute of Medical Research
Department Stem Cell Regulation Unit
Lab Walkley
Street address 9 Princes st, Fitzroy
City Melbourne
State/province VIC
ZIP/Postal code 3065
Country Australia
Platforms (1)
GPL11533 [MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version]
Samples (11)
GSM1534547 MEP_Hoxa1_r1
GSM1534548 MEP_Hoxa1_r2
GSM1534549 MEP_Hoxa1_r4
BioProject PRJNA265844

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62853_RAW.tar 42.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap