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Series GSE84703 Query DataSets for GSE84703
Status Public on Jan 18, 2017
Title Chromatin remodelling factor SMARCD2 (BAF60B) regulates transcriptional networks controlling early and late differentiation of neutrophil granulocytes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Differentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia.
 
Overall design We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates
Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers:
CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP)
CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP)
CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)


 
Contributor(s) Witzel M, Ziegenhain C
Citation(s) 28369036
Submission date Jul 21, 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 (64)
GSM2247821 HT19.1
GSM2247822 HT19.3
GSM2247823 HT19.4
Relations
BioProject PRJNA330860
SRA SRP079238

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
GSE84703_CMP.counts.txt.gz 334.5 Kb (ftp)(http) TXT
GSE84703_GMP.counts.txt.gz 418.3 Kb (ftp)(http) TXT
GSE84703_MEP.counts.txt.gz 295.3 Kb (ftp)(http) TXT
GSE84703_RAW.tar 3.2 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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