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Series GSE90552 Query DataSets for GSE90552
Status Public on Nov 01, 2017
Title In Vivo Chemical Screen Nominates Valproic Acid as Pharmacologic Modulator of Hematopoietic Stem and Progenitor Cell Activity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties.
 
Overall design Gene expression analysis of in vitro expanded human HSPCs (CD34+ cells) by valproic acid
 
Contributor(s) Arulmozhivarman G, Alexopoulou D, Dahl A, Bornhäuser M
Citation(s) 28935977
Submission date Nov 26, 2016
Last update date May 15, 2019
Contact name Guruchandar Arulmozhivarman
E-mail(s) guruschandar.arulmozhiv@crt-dresden.de
Organization name TU Dresden - Faculty of Medicine
Department Hematology department
Lab Dresden Stem Cell Lab
Street address Fetscherstraße 74
City Dresden
ZIP/Postal code 01307
Country Germany
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (8)
GSM2406734 PBS_1
GSM2406735 PBS_2
GSM2406736 PBS_3
Relations
BioProject PRJNA355003
SRA SRP093978

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
GSE90552_featureCounts.hg38.e81.csv.gz 3.4 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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