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Series GSE168207 Query DataSets for GSE168207
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.
Overall design Comparison of gene expression in freshly isolated wt and flt3L-/- SP-CPCs.
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
Organization name University of Basel
Department Departement of Biomedicine
Street address Hebelstrasse 20
City Basel
State/province BS
ZIP/Postal code 4053
Country Switzerland
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM5133961 CPC_Bl6N_1
GSM5133962 CPC_FLKO_3
GSM5133963 CPC_Bl6N_2
BioProject PRJNA706448
SRA SRP309179

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE168207_gene_counts.tsv.gz 416.5 Kb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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