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Nucleoplasmic ZNF467 condensates boost hematopoietic stem cell engraftment via ICAM1-mediated mechanical
Yandan Chen1,2, Jinghao Shen3,4, Zaisheng Lin5
1Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine and State Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.
Blood
|February 11, 2026
Summary
Mechanical robustness, regulated by ZNF467, is key for hematopoietic stem cell (HSC) engraftment. Enhancing ZNF467’s function improves HSC regenerative capacity and transplantation outcomes.
Area of Science:
- Stem cell biology
- Biotechnology
- Hematology
Background:
- Hematopoietic stem cell (HSC) transplantation is vital for treating blood disorders but limited by poor engraftment.
- Understanding intrinsic HSC properties is crucial for improving transplantation efficacy.
Purpose of the Study:
- To identify intrinsic factors determining HSC regenerative capacity.
- To investigate the role of mechanical properties in HSC function and engraftment.
Main Methods:
- Integrative biomechanical and transcriptomic profiling of human HSCs and multipotent progenitors (MPPs).
- Functional assays assessing HSC mechanical integrity and engraftment post-ZNF467 manipulation.
- Analysis of ICAM1 expression and phase separation activity of ZNF467.
Main Results:
- Mechanical robustness distinguishes HSCs from MPPs.
- ZNF467 is identified as a key regulator of HSC mechanical integrity; its loss impairs engraftment.
- An engineered ZNF467 variant enhanced mechanical strength and HSC engraftment, partly via ICAM1 upregulation.
Conclusions:
- Mechanical properties are critical determinants of stem cell identity and function.
- ZNF467-mediated biomechanical regulation offers novel strategies for enhancing HSC engraftment and transplantation success.
- Targeting ZNF467 and ICAM1 may improve regenerative medicine approaches.
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