2026-04-17T03:43:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1854532025-12-04T19:12:15Zcom_2072_1057col_2072_478858col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Melendez, Elena author Chondronasiou, Dafni author Mosteiro, Lluc author Martínez de Villarreal, Jaime author Fernández Alfara, Marcos author Lynch, Cian J. author Grimm, Dirk author Real, Francisco X. author Alcamí, José author Climent Vidal, Núria author Pietrocola, Federico author Serrano Marugán, Manuel author 2022-05-09T07:53:46Z 2022-05-09T07:53:46Z 2022-04-14 2022-05-06T10:17:27Z The ectopic expression of transcription factors Oct4, Sox2, Klf4 and Myc (OSKM) enables reprogramming of differentiated cells into pluripotent embryonic stem cells. Methods based on partial and reversible in vivo reprogramming are a promising strategy for tissue regeneration and rejuvenation. However, little is known about the barriers that impair reprogramming in an in vivo context. We report that natural killer (NK) cells significantly limit reprogramming, both in vitro and in vivo. Cells and tissues at the intermediate states of reprogramming upregulate the expression of NK activating ligands, such as MULT1 and ICAM1. NK cells recognize and kill partially reprogrammed cells in a degranulation-dependent manner. Importantly, in vivo partial reprogramming is strongly reduced by adoptive transfer of NK cells, whereas it is significantly improved by depletion of NK cells. Notably, in the absence of NK cells, the pancreatic organoids derived from OSKM-expressing mice are remarkably large, suggesting the generation of cells with progenitor properties. We conclude that NK cells pose an important barrier for in vivo reprogramming, and this concept may apply to other contexts of transient cellular plasticity. Cèl·lules mare embrionàries Cèl·lules K Sistema immunitari Embryonic stem cells Killer cells Immune system Natural killer cells act as an extrinsic barrier for in vivo reprogramming