Mechanical stimuli generated by blood flow regulate hematopoiesis in Drosophila

What is it about?

Hematopoietic stem and progenitor cells (HSPCs) in the vertebrate bone marrow give rise to blood cells. The maintenance of HSPCs depends on signals from their tissue microenvironment, called "niche". In a paper published in the journal PNAS, scientists have shown using the Drosophila model how biomechanical forces produced by blood flow activate a mechano-dependent ion channel and thus regulate the control of hematopoiesis. Hematopoiesis or the production of blood/immune cells is an important process in all metazoans and is a fundamental facet of immunity. The importance of biomechanical signals in the regulation of HSPCs, and the molecular mechanisms that transduce these mechanical signals into gene regulation remain largely unknown. In this study, the scientists found that in Drosophila, the mechanical stimulus, related to the blood flow that is generated during heart tube contractions, regulates hematopoiesis. They also established a gene regulatory network by which biomechanical forces regulate hematopoiesis. Blood flow, by exerting biomechanical forces on cells in the vascular niche, activates the mechanosensitive Piezo ion channel, which leads to regulation of the intracellular Ca2+ level in these cells. Ca2+ regulates the activity of the Notch signaling pathway that inhibits the production of the fibroblast growth factor (FGF) pathway ligand in the vascular niche. Secretion of this ligand by cells in the vascular niche activates FGF signaling in hematopoietic progenitors and thus ensures their maintenance.

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Photo by ANIRUDH on Unsplash

Photo by ANIRUDH on Unsplash

Why is it important?

This study opens the way to a better understanding of the role played by biomechanical forces on niche cells to control hematopoiesis. The deciphering at the molecular level of the mechanisms involved in Drosophila, and the parallels with the control of hematopoiesis in mammals, opens new perspectives for basic and clinical research for a better understanding of the role of biomechanical forces on hematopoietic stem cell biology in homeostasis, aging and cancer.