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<p>Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to induce HSC proliferation and myelopoiesis. We show that shear stress induces PIEZO1-mediated ion currents and Ca<sup>2+</sup> influx in both mouse and human HSCs, with downstream effects on proliferation and myeloid differentiation mediated via JAM3 and CAPN2 pathways. GsMTx4, a PIEZO1 antagonist, attenuated inflammation-induced aging in mice by inhibiting HSC activation. These findings link the mechanical sensor PIEZO1 to HSC proliferation and myeloid differentiation via multi-tiered signaling, highlighting its role in accelerating inflammation-induced aging.</p>

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Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging

  • 期刊论文

  • 发表日期：

    2026年1月2日

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  • Tongyao Shang,
  • Li Zhao,
  • Shibo Ying,
  • Lida Su,
  • Yue Yang,
  • Jiadong Liu,
  • Yingying Wang,
  • Jipeng Xue,
  • Cheng Cheng,
  • Yixin Wu,
  • Shiyao Chen,
  • Hongmei Dong,
  • Xuequn Chen,
  • Hailin Ma,
  • Qi Zhang,
  • Tingbo Liang,
  • Wei Yang,
  • Ye Feng,
  • Marong Fang,
  • Xinjiang Lu

摘要

Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to induce HSC proliferation and myelopoiesis. We show that shear stress induces PIEZO1-mediated ion currents and Ca2+ influx in both mouse and human HSCs, with downstream effects on proliferation and myeloid differentiation mediated via JAM3 and CAPN2 pathways. GsMTx4, a PIEZO1 antagonist, attenuated inflammation-induced aging in mice by inhibiting HSC activation. These findings link the mechanical sensor PIEZO1 to HSC proliferation and myeloid differentiation via multi-tiered signaling, highlighting its role in accelerating inflammation-induced aging.