Activation of Piezo1 induces heterogeneity in LSK cells leading to HSC proliferation and myelopoiesis [scRNA-seq]

Bone marrow haematopoietic stem cells (HSCs) are mobilised into blood under various stresses. Although they are exposed to shear stress during circulation, the role of mechanical stimulation in regulating HSCs remains unknown. Piezo1, a mechanosensory ion channel, was implicated in regulation of haematopoietic cells. We analysed the transcriptional heterogeneity of LSK cells from mice treated with the Piezo1 agonist Yoda1 for 2 weeks. Our study demonstrated that activation of Piezo1 promoted HSC proliferation and differentiation toward the myeloid lineage, as evidenced by an increase in HSC numbers and the upregulation of myeloid transcription factors. Overall design: LSK cells were sorted from the bone marrow of control and Yoda1-treated mice.