Adult cardiac-resident MSC-like stem cells with a proepicardial origin

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Developmental Biology

Background:

• Colony-forming units-fibroblasts (CFU-Fs) are analogous to bone marrow (BM) mesenchymal stem cells (MSCs).
• The relationship between BM-derived and organ-specific CFU-Fs during homeostasis and repair is not well understood.
• Understanding the origin and behavior of cardiac-resident CFU-Fs (cCFU-Fs) is crucial for regenerative medicine.

Purpose of the Study:

• To characterize the origin and behavior of adult cardiac-resident CFU-Fs (cCFU-Fs).
• To investigate the potential interchange between BM-derived and cCFU-Fs in various physiological and pathological conditions.
• To explore the developmental origins and differentiation potential of cCFU-Fs.

Main Methods:

• CRE lineage tracing and embryo analysis to determine cCFU-Fs origin.
• Bone marrow transplantation chimeras to assess cell interchange.
• Analysis of CFU-Fs from different organs (cardiac, aortic, BM) for distinct lineage signatures.

Main Results:

• Adult cCFU-Fs reside in a perivascular, adventitial niche and exhibit broad in vitro and in vivo differentiation potential.
• CRE lineage tracing identified a proepicardial origin for cCFU-Fs.
• No interchange between BM and cCFU-Fs was observed after aging, myocardial infarction, or BM stem cell mobilization.
• BM, cardiac, and aortic CFU-Fs displayed distinct CRE lineage signatures, indicating separate developmental origins.

Conclusions:

• Cardiac-resident CFU-Fs originate from the proepicardium, distinct from bone marrow-derived CFU-Fs.
• The lack of interchange and diverse developmental origins suggest inherent differentiation biases in different CFU-F populations.
• These findings provide insights into the functional heterogeneity of CFU-Fs and their potential roles in tissue repair.