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| 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 [CITE-seq-GMP-WT] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| 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.
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| |
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| Overall design |
Single cell RNA seq of wild-type Modified GMP
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| |
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| Contributor(s) |
Muench DE, Chetal K, Salomonis N, Grimes HL |
| Citation(s) |
32494068 |
| |
| Submission date |
Sep 24, 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 |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (3) |
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| 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 |
PRJNA492890 |
| SRA |
SRP162603 |
