Biomechanical force in blood development: Extrinsic physical cues drive pro-hematopoietic signaling

• Mechanical cues in the niche evolve during hematopoietic ontogeny to accommodate changing needs of the blood system.
• Vascular forces contribute to several stages of hematopoiesis, including definitive HSC emergence.
• Shear stress activates intracellular signaling critical for blood development.
• Current methodologies for in vitro generation of hematopoietic cells can be improved by a better understanding of regulatory biophysical cues.

The hematopoietic system is dynamic during development and in adulthood, undergoing countless spatial and temporal transitions during the course of one's life. Microenvironmental cues in the many unique hematopoietic niches differ, characterized by distinct soluble molecules, membrane-bound factors, and biophysical features that meet the changing needs of the blood system. Research from the last decade has revealed the importance of substrate elasticity and biomechanical force in determination of stem cell fate. Our understanding of the role of these factors in hematopoiesis is still relatively poor; however, the developmental origin of blood cells from the endothelium provides a model for comparison. Many endothelial mechanical sensors and second messenger systems may also determine hematopoietic stem cell fate, self renewal, and homing behaviors. Further, the intimate contact of hematopoietic cells with mechanosensitive cell types, including osteoblasts, endothelial cells, mesenchymal stem cells, and pericytes, places them in close proximity to paracrine signaling downstream of mechanical signals. The objective of this review is to present an overview of the sensors and intracellular signaling pathways activated by mechanical cues and highlight the role of mechanotransductive pathways in hematopoiesis.