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Series GSE84993 Query DataSets for GSE84993
Status Public on Dec 16, 2016
Title Niche WNT5A regulates expression of the actin regulatory pathway in regenerating repopulating hematopoietic stem cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We here show that the niche regulates the quality of the hematopoietic stem cells (HSCs) that are regenerated after transplantation. We find that a reduced level of Wnt5a in the niche regenerates dysfunctional HSCs, which do not successfully engraft secondary recipients. In particular, RNA sequencing shows a dysregulated Zeb1-associated gene expression of multiple genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of these genes results in reduced ability to direct polarized F-actin localization, leading to defects in adhesion, migratory behavior and homing to the bone marrow of secondary recipients. Our study further shows that the Wnt5a-haploinsufficient environment similarly affects BCR-ABLp185+ cells, which, in 42% of the studied recipients, fail to generate leukemia and, in the remaining cases, fail to transfer leukemia to secondary hosts. Thus, we show that Wnt5a in the niche is required to regenerate HSCs and leukemic cells with functional ability to rearrange the actin cytoskeleton which is required for successful engraftment.
 
Overall design Hematopoietic stem cells are regenerated in WT or Wnt5a-haploinsufficient niches. We profile LSK hematopoiteic stem cells after transplantation and three cell populations from the niche environment: endothelial cells (EC), osteoblastic cells (OBC), and mesenchymal cells (MSC)
Web link https://dx.doi.org/10.1084/jem.20151414
 
Contributor(s) Ziegenhain C, Schreck C, Oostendorp RA
Citation(s) 27998927
Submission date Jul 29, 2016
Last update date May 15, 2019
Contact name Christoph Ziegenhain
E-mail(s) ziegenhain@bio.lmu.de
Organization name Ludwig-Maximilians University Munich
Department Department Biology II
Lab Anthropology & Human genomics
Street address GroƟhaderner Str. 2
City Martinsried
State/province Bavaria
ZIP/Postal code 82152
Country Germany
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (29)
GSM2255634 8481Tx_WT
GSM2255635 8531Tx_WT
GSM2255636 8551Tx_WT
Relations
BioProject PRJNA335842
SRA SRP080326

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
GSE84993_Smartseq_LSK_count_table.txt.gz 420.7 Kb (ftp)(http) TXT
GSE84993_UMIseq_niche_cells_UMItable.txt.gz 184.0 Kb (ftp)(http) TXT
GSE84993_UMIseq_niche_cells_barcode_annotation.txt.gz 213 b (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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