Discovery of NRG1-VII: the myeloid-derived class of NRG1.

Autor: Berrocal-Rubio MA; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Pawer YDJ; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Dinevska M; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia., De Paoli-Iseppi R; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Widodo SS; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia., Gleeson J; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Rajab N; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., De Nardo W; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Hallab J; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Li A; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Mantamadiotis T; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.; Department of Microbiology and Immunology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Clark MB; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia., Wells CA; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia. wells.c@unimelb.edu.au.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Aug 29; Vol. 25 (1), pp. 814. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1186/s12864-024-10723-2
Abstrakt: The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.
(© 2024. The Author(s).)
Databáze: MEDLINE
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