2. Academic Validation
  3. Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging

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

  • Nat Aging. 2026 Jan;6(1):88-107. doi: 10.1038/s43587-025-01039-1.
Tongyao Shang # 1 2,  Li Zhao # 3,  Shibo Ying # 4,  Lida Su 5,  Yue Yang 1,  Jiadong Liu 1,  Yingying Wang 6 7,  Jipeng Xue 1,  Cheng Cheng 1,  Yixin Wu 1 8,  Shiyao Chen 1,  Hongmei Dong 9,  Xuequn Chen 10,  Hailin Ma 11 12,  Qi Zhang 13 14,  Tingbo Liang 13 14,  Wei Yang 15 16,  Ye Feng 17,  Marong Fang 18,  Xinjiang Lu 19
Affiliations

Affiliations

  • 1 Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 School of Civil Engineering and Architecture, Zhejiang University of Science & Technology, Hangzhou, China.
  • 4 Hangzhou Medical College, Hangzhou, China.
  • 5 Neuroscience Care Unit, Key Laboratory of Multiple Organ Failure of Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Department of Biophysics and Neurology, Center for Membrane Receptors and Brain Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
  • 7 Guizhou University Medical College, Guiyang, China.
  • 8 School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
  • 9 The 941st Hospital of Joint Logistics Support Force of PLA, Xining, China.
  • 10 Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
  • 11 Key Laboratory of High Altitudes Brain Science and Environmental Acclimation, Xizang University, Lhasa, China.
  • 12 Plateau Brain Science Research Center, Xizang University, Lhasa, China.
  • 13 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 14 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 15 Department of Biophysics and Neurology, Center for Membrane Receptors and Brain Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China. [email protected].
  • 16 Guizhou University Medical College, Guiyang, China. [email protected].
  • 17 Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  • 18 Orthopedics Department, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Centre for Child Health, Hangzhou, China. [email protected].
  • 19 Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 41482519 DOI: 10.1038/s43587-025-01039-1
Abstract

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.

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