Loss of TET2 in human hematopoietic stem cells alters the development and function of neutrophils.

Autor:	Huerga Encabo H; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: hector.encabo@crick.ac.uk., Aramburu IV; Laboratory of Antimicrobial Defence, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Garcia-Albornoz M; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Piganeau M; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Wood H; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Song A; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Ferrelli A; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Sharma A; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Minutti CM; Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Domart MC; Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Papazoglou D; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Gurashi K; Division of Cancer Sciences, The University of Manchester, Manchester, UK., Llorian Sopena M; Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Goldstone R; Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Fallesen T; Advanced Light Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Wang Q; Laboratory of Antimicrobial Defence, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Ariza-McNaughton L; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Wiseman DH; Division of Cancer Sciences, The University of Manchester, Manchester, UK., Batta K; Division of Cancer Sciences, The University of Manchester, Manchester, UK., Gupta R; Haematology Stem Cell Group, UCL Cancer Institute, London, UK., Papayannopoulos V; Laboratory of Antimicrobial Defence, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: veni.papayannopoulos@crick.ac.uk., Bonnet D; Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: dominique.bonnet@crick.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2023 Jun 01; Vol. 30 (6), pp. 781-799.e9.
DOI:	10.1016/j.stem.2023.05.004
Abstrakt:	Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Using genetic engineering of human HSCs (hHSCs) and transplantation in immunodeficient mice, we describe how a commonly mutated gene in CH, TET2, affects human neutrophil development and function. TET2 loss in hHSCs produce a distinct neutrophil heterogeneity in bone marrow and peripheral tissues by increasing the repopulating capacity of neutrophil progenitors and giving rise to low-granule neutrophils. Human neutrophils that inherited TET2 mutations mount exacerbated inflammatory responses and have more condensed chromatin, which correlates with compact neutrophil extracellular trap (NET) production. We expose here physiological abnormalities that may inform future strategies to detect TET2-CH and prevent NET-mediated pathologies associated with CH. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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