On Friday April 5th, 2024 Riley Leonard successfully defended his PHD thesis titled  "From Cardiac Development to Regeneration: A New Murine Model to Study the Role of Cardiogenic Transcription Factors"

Today, malformations of the heart called Congenital Heart Defects (CHDs) are the most common birth defect, occurring 1 in 100 live births. On the opposite end, cardiovascular disease (CVD) in adults is the leading cause of mortality in the world. Like development, the understanding of how CVDs arise has been an area of active study. In both, research has provided the basis for how the heart forms and functions. 

Here, using a new mouse model to study embryonic cardiac development, has revealed an unfound role for transcription factors (TFs) Tbx5, Gata4, and Mef2c. These factors share a common microRNA regulator, the miR-200 family. In the PMIS-miR-200 mice caused increased expression of Tbx5, Gata4, and Mef2c during heart development. Employment of single nuclei (sn) Multi-Omic sequencing of embryonic hearts, found a new cardiomyocyte cell population. Bioinformatic analysis revealed this new population to possess “progenitor-like” qualities. Further investigation of the cardiomyocyte population unraveled how inhibiting miR-200 allows its expansion and regenerative capabilities. 

In a mouse model of ischemic injury, PMIS-miR-200c hearts possessed rapid, sustained, and efficient cardiac regeneration. By 3 weeks following the injury, PMIS-miR-200c mice had recovered cardiac function and could be described as “too good to be true.” Molecularly, inhibiting miR-200c increased express of Tbx5, Gata4, and Mef2c and the “progenitor-like” population of cardiomyocytes found in development. The ability for PMIS-miR-200c mice to regenerative post-MI, opens to door to potential clinical therapeutic for patients. 

Congratulations Riley!