Background Although cardiac c-kit+ cells are being tested in clinical trials, the circumstances that determine lineage differentiation of c-kit+ cells in vivo are unknown. Recent findings suggest endogenous cardiac c-kit+ cells rarely contribute cardiomyocytes to the adult heart. We assessed whether various pathological stimuli differentially affect the eventual cell fates of c-kit+ cells. Methods We employed single cell sequencing and genetic lineage tracing of c-kit+ cells to determine whether various pathologic stimuli would result in different fates of c-kit+ cells. Results Single cell sequencing of cardiac CD45−c-kit+ cells showed innate heterogeneity, indicative of the existence of vascular and mesenchymal c-kit+ cells in normal hearts. Cardiac pressure overload resulted in a modest increase in c-kit derived cardiomyocytes with significant increases in the numbers of endothelial cells and fibroblasts. Doxorubicin-induced (DOX) acute cardiotoxicity did not increase c-kit derived endothelial cell fates but instead induced cardiomyocyte differentiation. Mechanistically, DOX induced DNA damage in c-kit+ cells resulted in expression of p53. Inhibition of p53 blocked cardiomyocyte differentiation in response to DOX, while the small molecule RITA induced stabilization of p53 was sufficient to increase c-kit derived cardiomyocyte differentiation. Conclusion These results demonstrate that different pathologic stimuli induce different cell fates of c-kit+ cells in vivo. Although the overall rate of cardiomyocyte formation from c-kit+ cells is still below clinically relevant levels, we show that p53 is central to the ability of c-kit+ cells to adopt cardiomyocyte fates, which could lead to the development of strategies to preferentially generate cardiomyocytes from c-kit+ cells.

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Helping student service members and veterans (SSM/Vs) earn a college degree is central to supporting them post-service. Yet, this generation of SSM/Vs faces challenges in higher education, including problems adapting, poor health, and administrative constraints, contributing to worsened academic outcomes and a sense of isolation on campus. This monograph synthesizes research on the challenges facing SSM/Vs. It also frames common aspects of successful programs aiding SSM/Vs as three areas for intervention: how administrators and faculty can create a welcoming campus for SSM/Vs; ways universities can create support systems for SSM/V social, health, and academic success; and engaging community partnerships to enable these efforts. Whether SSM/Vs overcome their challenges and unlock their strengths is contingent on opportunities provided within the school itself, and by its faculty, administrators, students, and community. Central to these efforts should be the goal of inclusivity enhancement, community building, and reduction of health-related dysfunction among SSM/Vs.

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