CSB Seminar Series – Felix Gunawan, PhD – Cell and Systems Biology, University of Toronto

CSB Departmental Seminar

Felix Gunawan, PhD

Cell and Systems Biology, University of Toronto

TITLE:

Elucidating the cellular and molecular mechanisms underlying cardiac tissue morphogenesis

ABSTRACT:

The heart is a biomechanical engine, where every beat generates forces that feeds back and shape how cells grow, differentiate, and organize into functional tissues. While the myocardium has long captured attention as the contractile muscle of the heart, the inner lining or endocardium remains relatively overlooked. This specialized endothelial layer directly senses blood flow and converts mechanical cues into cellular behaviors, positioning it as a key regulator of both heart development and hematopoiesis. By probing how the endocardium integrates physical forces with molecular signaling, we aim to uncover fundamental principles of mechanobiology with relevance beyond the cardiovascular system.
We have uncovered how endocardial cells generate cardiac valves that prevent retrograde blood flow. Using live imaging and genetic tools in zebrafish, we show that valve formation is orchestrated through collective endocardial migration, differentiation into fibroblast-like cells, and secretion of a specialized extracellular matrix. Our recent work shows that the forming valve endocardium deposits a basement membrane that restricts overproliferation, controls valve shape and stiffness, and sustains biomechanical integrity. Basement membrane disorganization led to enlarged valves that fail to prevent retrograde blood flow, leading to defective circulation and death. Strikingly, we find that heartbeat-driven forces provide feedback that maintains basement membrane levels, highlighting a direct interplay between flow dynamics and tissue morphogenesis.
Our work further uncovers a surprising and previously unrecognized role for the cardiac endothelium as a niche for hematopoietic stem and progenitor cells (HSPCs). Using high resolution confocal and spinning disk imaging, we identified HSPCs attached to the endocardium, where they persist in direct contact with flowing blood. Lineage-tracing experiments revealed that these cells derive not only from the aorta, which is the canonical source of hematopoietic stem cells, but also from the endocardium itself. Functionally, we found that blocking red blood cell production increases cardiac-residing HSPCs, suggesting that the heart provides a dynamic reservoir that adapts to systemic demands. This discovery positions the endocardium as a hematopoietic resident tissue uniquely exposed to biomechanical forces. Ongoing work is investigating the function of the endocardial-residing HSPCs during normal development and under stress conditions.
Together, our findings position the endocardium as a central integrator of mechanical cues and cellular plasticity, with implications for understanding congenital heart disease, valve degeneration, and hematopoietic resilience.

HOST: John Calarco

LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432

LIVESTREAM LINK: https://csb.utoronto.ca/live-stream/