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There has been great interest in the potential role of cKit+ cells as mediators of heart regeneration. To explore this issue, van Berlo et al1 recently used genetic lineage tracing in the mouse to mark cKit+ cells. When we looked at tissues from these mice, the lungs were green, the gastrointestinal tract was green, the bone marrow was green, and the testis were green, but the heart was not. This was a surprising finding, given the extensive literature implicating cKit+ cells in regeneration of the heart. In-depth microscopic analysis revealed that cardiac endothelial cells were abundantly labeled (as much as 50%), but only a few rare myocytes were green fluorescent protein (GFP+) (maximum of 0.03%). The report contained extensive control experiments to validate all observations and suggested the simplest conclusion: that there were few adult cardiac myocytes derived from cKit+ progeny. Below we highlight the key issues and attempt to bring clarity to this field in light of a recent commentary published in Circulation Research by Dr Nadal-Ginard et al2 that question the conclusions and some theoretical aspects of the study by van Berlo et al.The specific points in response to this commentary are as follows:This is a …

Letter by Molkentin Regarding Article, “The Absence of Evidence Is Not Evidence of Absence: The Pitfalls of Cre Knock-Ins in the c-Kit Locus”