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Series GSE120404 Query DataSets for GSE120404
Status Public on Apr 06, 2020
Title A neutropenia-associated transcription factor mutation differentially impacts target genes in the cell-states traversed during granulocyte specification and commitment [Gfi1-R412X-HMZ]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Advances in genetics and sequencing have lead to a deluge of disease-associated and disease-causing genetic alterations. Resolving causality between genetics and disease requires generating accurate models for molecular dissection; however, the rapid expansion of single-cell landscapes presents a major challenge to accurate comparisons between mutants and their wild type equivalents. Here, we generated mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the Growth factor independent-1 (GFI1) transcription factor. To delineate the impact of SCN mutations, we first generated single-cell references for granulopoietic genomic states with linked epitopes, then developed a new computational approach to align mutant cells to their wild-type equivalent and derive differentially expressed genes. Surprisingly, the majority of differentially expressed GFI1-target genes are sequentially altered as cells traverse successive states. These cell-state-specific insights facilitated genetic rescue of granulocytic specification but not post-commitment defects in the expression of innate-immune effectors, providing regulatory insights into granulocyte dysfunction.
 
Overall design Single cell RNA seq of Gfi1-R412X mutant GMP subpopulations
 
Contributor(s) Muench DE, Chetal K, Salomonis N, Grimes HL
Citation(s) 32494068
Submission date Sep 25, 2018
Last update date Jul 07, 2020
Contact name H. Leighton Grimes
E-mail(s) Lee.Grimes@cchmc.org
Phone 513-636-6089
Organization name Cincinnati Childrens Hospital Medical Center
Department Immunobiology
Lab Grimes
Street address 3333 Burnet Ave. MLC 7038
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (92)
GSM3400004 Gfi1-R412X-HMZ_GMP_Cell42
GSM3400005 Gfi1-R412X-HMZ_GMP_Cell1
GSM3400006 Gfi1-R412X-HMZ_GMP_Cell2
This SubSeries is part of SuperSeries:
GSE120409 A neutropenia-associated transcription factor mutation differentially impacts target genes in the cell-states traversed during granulocyte specification and commitment
Relations
BioProject PRJNA493006
SRA SRP162509

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
GSE120404_exp.R412X-HMZ.txt.gz 2.2 Mb (ftp)(http) TXT
GSE120404_groups.R412X-HMZ.txt.gz 376 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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