Key result
SM22α-Cre-mediated recombination occurs in resting cardiac fibroblasts and hematopoietic cell lineages, including hematopoietic precursor cells, indicating a need for caution when using this model.
Why the study?
It was unknown whether SM22alpha-Cre recombination takes place in non-cardiomyocytes in the heart.
SM22α-Cre activity in resting fibroblasts and myeloid cells cautions against VSMC-only assumptions; leaves open precise lineage tracing in cardiovascular models.
The Cre-loxP system has been widely used for cell- or organ-specific gene manipulation, but it is important to precisely understand what kind of cells the recombination takes place in. Smooth muscle 22α (SM22α)-Cre mice have been utilized to alter genes in vascular smooth muscle cells (VSMCs), activated fibroblasts or cardiomyocytes (CMs). Moreover, previous reports indicated that SM22α-Cre is expressed in adipocytes, platelets or myeloid cells. However, there have been no report of whether SM22α-Cre recombination takes place in nonCMs in hearts. Thus, we used the double-fluorescent Cre reporter mouse in which GFP is expressed when recombination occurs. Immunofluorescence analysis demonstrated that recombination occurred in resting cardiac fibroblasts (CFs) or macrophages, as well as VSMCs and CMs. Flow cytometry showed that some CFs, resident macrophages, neutrophils, T cells, and B cells were positive for GFP. These results prompted us to analyze bone marrow cells, and we observed GFP-positive hematopoietic precursor cells (HPCs). Taken together, these results indicated that SM22α-Cre-mediated recombination occurs in resting CFs and hematopoietic cell lineages, including HPCs, which is a cautionary point when using SM22α-Cre mice.
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Ikeda et al. (2022) studied Healthy (steady-state). SM22α-Cre recombination was evaluated on GFP expression in specific cell types (cardiac fibroblasts, macrophages, hematopoietic precursor cells). SM22α-Cre-mediated recombination occurs in resting cardiac fibroblasts and hematopoietic cell lineages, including hematopoietic precursor cells, indicating a need for caution when using this model.
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