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

Differentiation. 2013 Oct;86(3):92-103. doi: 10.1016/j.diff.2013.06.004. Epub 2013 Jul 12.


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.

Keywords: ADAM; AGM; Biomechanical force; CXCR; CaSR; Cellular microenvironment; DAG; Dll; ECM; FA; FAK; FZD; Flk-1; Frizzled; G protein-coupled receptor; GPCR; HSC; HSPC; HUVEC; Hematopoietic stem cells; Hemogenic endothelium; ILK; IP3; MAPK; Mechanotransduction; NICD; NOS; Notch intracellular domain; PGE2; PI3K; PKA; PKD; PLC; ROCK; Rho-associated protein kinase; S1P; S1PR/EDG1; SDF1; Shear stress; TRPV4; a disintegrin and metalloprotease; aorta-gonad-mesonephros; calcium sensing receptor; chemokine C-X-C motif receptor; delta-like; diacylglycerol; extracellular matrix; fetal liver kinase-1; focal adhesion; focal adhesion kinase; hematopoietic stem and progenitor cells; hematopoietic stem cell; human umbilical vein endothelial cells; inositol triphosphate; integrin linked kinase; mitogen activated protein kinase; nitric oxide synthase; phosphatidylinositide 3-kinase; phospholipase C; polycystin; prostaglandin E2; protein kinase A; sphingosine 1-phosphate; sphingosine 1-phosphate receptor; stromal derived factor 1; transient receptor potential vallinoid type 4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Mechanotransduction, Cellular*
  • Stem Cell Niche
  • Stress, Mechanical