Allen Yesin

All Publications

• Nuclear mechanobiology rules immune cells' functions: from differentiation to cell trafficking and pathogen killing. Nucleus (Austin, Tex.) Renkawitz, J., Yesin, A., Kroll, J., Cabral, A. T., D'Annunzio, S., Thiam, H. R. 2026; 17 (1): 2590843

  Abstract

  The immune system functions within tissue microenvironments of mechanical and geometrical constraints. Within these constraints, immune cells must rapidly move and execute effector functions to regulate innate and adaptive immunity. Here, we review the impact of nuclear mechanobiology on immune cell functionality. We define how non-genetic physical properties of the nucleus such as shape, stiffness and deformability are regulated and directly impact immune cell functions ranging from trafficking routes to pathogen killing. We highlight that studying immune cells allowed breakthroughs in understanding how the nucleus acts as a sensor for spatial constraints, as a break or enabler for cell migration, and as an extracellular trap to kill pathogens. Further, we discuss the unknowns of nuclear mechanobiology and consider the impact of chromatin, condensates, and nuclear membrane components. Together, this review provides an overarching framework of the cellular, physical, and immunological principles of nuclear mechanobiology in immune cells.

  View details for DOI 10.1080/19491034.2025.2590843

  View details for PubMedID 41495604

• Nuclear remodeling and optimal migration emerge early, and constriction-passage progressively improves during hematopoietic stem cells to neutrophils differentiation. bioRxiv : the preprint server for biology Yesin, A., Outlaw, K., Sanchez-Flores, R., Doucoure, A., Hüttenhain, R., Thiam, H. R. 2026

  Abstract

  Neutrophils' ability to rapidly and efficiently migrate through narrow pores in tissues is essential for host defense and is proposed to depend on their multilobulated and deformable nucleus. When during neutrophil differentiation does optimal migration and its proposed nuclear determinants emerge, and whether they are intrinsic to progenitors, is unclear in part because of the scarcity of tractable models of human neutrophils and their progenitors. Here, we optimized a CD34+ hematopoietic stem cell (HSC) to neutrophil differentiation pipeline to generate millions of mature neutrophils (HSC-neutrophils) that recapitulate the surface markers, proteome, ROS production and NETosis of primary human blood-derived neutrophils, better than the widely used HL60-derived neutrophils. Comparative proteomics across differentiation showed that HSC-neutrophils become translationally repressed while acquiring immune functions and actin-related processes. Quantitative microscopy and proteomics showed that nuclear multilobulation occurs at the granulocyte progenitors-early neutrophils transition and is accompanied by drastic remodeling of nuclear envelope composition (increasing LBR, decreasing lamin A/C, B1/B2 and NUPs). Single nuclear envelope proteins only weakly correlate with nuclear multilobularity suggesting that an ensemble envelope state, rather than any one protein, sets nuclear shape. Using microfabricated devices with constrictions, we show that migration speed increases the most in early neutrophils; that the capacity to cross nucleus-deforming pores is continuously enhanced during differentiation; and that early neutrophils recover the best from such migration. We show that while mature neutrophils most effectively cross pores, they remain impaired. Our work resolves three features of neutrophils migration - speed, deformation through constrictions, and recovery from deformation - and maps when each emerges, opening the door to future mechanistic and engineering studies for modulating neutrophil migration in tissue-like microenvironments.

  View details for DOI 10.64898/2026.09.03.749278

  View details for PubMedID 42818534

  View details for PubMedCentralID PMC13622464

• In vitro generated neutrophils reveal high deformability is an emergent property Yesin, A., Flores, R., Thiam, H. CELL PRESS. 2026: 399a

  View details for Web of Science ID 001717743900206