Speaker: Pamela Wenzel, Professor of Integrative Biology and Pharmacology and Stem Cell and Regenerative Medicine at the University of Texas Health Science Center at Houston, McGovern Medical School 

Title: Mechanometabolism promotes hematopoietic stem cell specification

Abstract: Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the adult blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. In this talk, I describe our new data showing that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function that is essential for hematopoietic fate determination and adult engrafting potential. Shear stress remodels mitochondria by increasing transcription and translation of mitochondrial genes. Flow-responsive metabolic reprogramming depends upon mTOR activation and is stymied when ribosome activity or mTOR is blocked. Conversely, chemical induction of mTOR mimics the effects of force on mitochondria and blood reconstituting potential and also partially rescues hematopoiesis in heartbeat mutants in utero. These findings identify mechanometabolism as a determinant of HSC fate that could inform engineering of HSCs for disease modeling and treatment.

Hosts: Clyde Campbell and Raquel Espin Palazon, assistant professors in genetics, development and cell biology