Stem Cell Niches in the Adult Mouse Heart

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 24; pp. 9226 - 9231
• Main Authors: Urbanek, Konrad, Cesselli, Daniela, Rota, Marcello, Nascimbene, Angelo, De Angelis, Antonella, Hosoda, Toru, Bearzi, Claudia, Boni, Alessandro, Bolli, Roberto, Kajstura, Jan, Anversa, Piero, Leri, Annarosa
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13-06-2006; National Acad Sciences
• Series: From the Cover
• Subjects: Animals; Biological Sciences; Biomarkers - metabolism; Bone marrow; Cadherins; Cell growth; Cell Lineage; Cell nucleus; Connexins; Endothelial cells; Fibroblasts; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Heart; Heart - anatomy & histology; Integrins - metabolism; Laminin - genetics; Laminin - metabolism; Mice; Myocardium; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - physiology; Proteins; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600635103

Cardiac stem cells (CSCs) have been identified in the adult heart, but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and fibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs-lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of a4-integrin, which colocalizes with the α₂-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base-midregion of the ventricle.