 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 28, 2024 |
| Title |
In Fanconi Anemia, impaired accumulation of bone marrow neutrophils during emergency granulopoiesis induces hematopoietic stem cell stress |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Fanconi Anemia (FA) is an inherited disorder of DNA-repair caused by mutation in one of 20+ interrelated genes that repair intra-strand DNA crosslinks and rescue collapsed or stalled replication forks. The most common hematologic abnormality in FA is anemia, but progression to bone marrow failure (BMF), clonal hematopoiesis, or acute myeloid leukemia (AML) may also occur. In prior studies, we found that Fanconi DNA-repair is required for successful emergency granulopoiesis; the process for rapid neutrophil production during the innate immune response. Specifically, Fancc-/- mice did not develop neutrophilia in response to emergency granulopoiesis stimuli, but instead exhibited apoptosis of bone marrow hematopoietic stem cells (HSCs) and differentiating neutrophils. Repeated emergency granulopoiesis challenges induced BMF in most Fancc-/- mice, with AML in survivors. In contrast, we found equivalent emergency granulopoiesis-induced neutrophilia in Fancc-/-Tp53+/- mice and wild type (WT) mice, without BMF in either. Since bone marrow neutrophil accumulation triggers termination of emergency granulopoiesis, we hypothesize neutrophilia protects Fancc-/-Tp53+/- bone marrow from the stress of sustained inflammatory physiology, as experienced by Fancc-/- mice.
|
| |
|
| Overall design |
We find blocked neutrophil accumulation during emergency granulopoiesis in Wt, Fancc-/- and Fancc-/-Tp53+/- mice in vivo with Ly6G antibody injections. In these studies, emergency granulopoiesis was induced by injection of Alum (ovalbumin + aluminium chloride) with saline as a steady state control. Mice were assessed for bone marrow failure and leukemia during these treatments. Bone marrow from the mice was harvested at various time points after treatment. LSK cells were separated by flow cytometry and subjected to total RNA sequencing.
|
| |
|
| Contributor(s) |
Eklund E, Hu L, Patel P |
| Citation(s) |
38992437 |
| |
| Submission date |
May 09, 2024 |
| Last update date |
Aug 29, 2024 |
| Contact name |
Priyam Patel |
| E-mail(s) |
priyam.patel@northwestern.edu
|
| Organization name |
Northwestern University
|
| Department |
Quantitative Data Science Core
|
| Street address |
750 North Lake Shore Drive, Rubloff 11-146
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (38)
|
|
| Relations |
| BioProject |
PRJNA1109928 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267161_RAW.tar |
7.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...