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| Status |
Public on Nov 30, 2021 |
| Title |
Fms-like tyrosine kinase 3 (Flt3) contributes to a receptor tyrosine kinase signature regulating the cardiac side population |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Fms-like tyrosine kinase 3 (Flt3) is a regulator of hematopoietic progenitor cells. It is a target of tyrosine kinase inhibitors (TKIs) used for acute myeloid leukemia treatment. Flt3 and its ligand (Flt3L) are expressed in the heart and cardiac side effects occur under Flt3-targeting TKIs. Whether Flt3/Flt3L also regulate cardiac progenitor cells (CPCs), however, is not known. The cardiac side population (SP) is a pool of heterogenous CPCs that can give rise to all cardiac lineages, hence contributing to cardiovascular homeostasis. Here we show that SP-CPCs produce and are responsive to Flt3L. Compared to wild-type, SP-CPCs from flt3L-/- mice are less abundant, with less contribution of CD45-CD34+ cells, and lower expression of gene sets related to epithelial-to-mesenchymal transition, cardiovascular development and stem cell differentiation. Upon culturing and compared to wild-type, flt3L-/- Sca1+CD31- SP-CPCs show increased proliferation and less vasculogenic commitment, but differentiation can be induced in the presence of receptor tyrosine kinase-activating growth factors. The observed differences are associated with decreased microvascularisation and global systolic function of flt3L-/- hearts. Thus, Flt3 contributes to a receptor tyrosine kinase signature necessary for the maintenance and functionality of SP-CPCs. These findings have potential implications regarding cardiovascular side effects observed under TKI therapy.
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| Overall design |
Comparison of gene expression in freshly isolated wt and flt3L-/- SP-CPCs.
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| Contributor(s) |
Roux J, Verde GD, Kuster GM |
| Citation(s) |
34903561 |
| |
| Submission date |
Mar 03, 2021 |
| Last update date |
Jan 27, 2022 |
| Contact name |
DBM Bioinformatics Core Facility |
| Phone |
+41612073541
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| Organization name |
University of Basel
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| Department |
Departement of Biomedicine
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| Street address |
Hebelstrasse 20
|
| City |
Basel |
| State/province |
BS |
| ZIP/Postal code |
4053 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA706448 |
| SRA |
SRP309179 |
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