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

Tongyao Shang^#^{1

2}, Li Zhao^#³, Shibo Ying^#⁴, Lida Su⁵, Yue Yang¹, Jiadong Liu¹, Yingying Wang^{6

7}, Jipeng Xue¹, Cheng Cheng¹, Yixin Wu^{1

8}, Shiyao Chen¹, Hongmei Dong⁹, Xuequn Chen¹⁰, Hailin Ma^{11

12}, Qi Zhang^{13

14}, Tingbo Liang^{13

14}, Wei Yang^{15

16}, Ye Feng¹⁷, Marong Fang¹⁸, Xinjiang Lu¹⁹

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. yangwei@zju.edu.cn.
¹⁶ Guizhou University Medical College, Guiyang, China. yangwei@zju.edu.cn.
¹⁷ Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. pandafengye@zju.edu.cn.
¹⁸ Orthopedics Department, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Centre for Child Health, Hangzhou, China. fangmaro@zju.edu.cn.
¹⁹ Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. luxinjiang@zju.edu.cn.

^# Contributed equally.

PMID: 41482519
DOI: 10.1038/s43587-025-01039-1

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

Tongyao Shang et al. Nat Aging. 2026 Jan.

. 2026 Jan;6(1):88-107.

doi: 10.1038/s43587-025-01039-1. Epub 2026 Jan 2.

Authors

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. yangwei@zju.edu.cn.
¹⁶ Guizhou University Medical College, Guiyang, China. yangwei@zju.edu.cn.
¹⁷ Institute of Translational Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. pandafengye@zju.edu.cn.
¹⁸ Orthopedics Department, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Centre for Child Health, Hangzhou, China. fangmaro@zju.edu.cn.
¹⁹ Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. luxinjiang@zju.edu.cn.

^# Contributed equally.

PMID: 41482519
DOI: 10.1038/s43587-025-01039-1

Erratum in

Publisher Correction: Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging.
Shang T, Zhao L, Ying S, Su L, Yang Y, Liu J, Wang Y, Xue J, Cheng C, Wu Y, Chen S, Dong H, Chen X, Ma H, Zhang Q, Liang T, Yang W, Feng Y, Fang M, Lu X. Shang T, et al. Nat Aging. 2026 Feb;6(2):464. doi: 10.1038/s43587-026-01079-1. Nat Aging. 2026. PMID: 41606145 No abstract available.

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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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

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1. Jamieson, C. H. M. & Weissman, I. L. Stem-cell aging and pathways to precancer evolution. N. Engl. J. Med. 389, 1310–1319 (2023). - PubMed - PMC
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Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous