1. Αποθετήριο Παραδοτέων Υποτρόφων Δράσεων ΕΣΠΑ Τριτοβάθμιας Εκπαίδευσης 2017-2023
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3. Μεταδιδακτορικοί ερευνητές

Τύπος:	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus
Συγγραφέας:	[EL] Γρηγορίου, Μαρία[EN] Grigoriou, Maria [EL] Μπάνος, Άγγελος[EN] Banos, Aggelos [EL] Φίλια, Αναστασία[EN] Filia, Anastasia [EL] Παυλίδης, Παύλος[EN] Pavlidis, Pavlos [EL] Γιαννούλη, Σταυρούλα[EN] Giannouli, Stavroula [EL] Καραλή, Βασιλική[EN] Karali, Vassiliki [EL] Νικολόπουλος, Διονύσης[EN] Nikolopoulos, DIonysis [EL] Πιέτα, Αντιγόνη[EN] Pieta, Antigone [EL] Μπερτσιάς, Γεώργιος[EN] Bertsias, George [EL] Βεργίνης, Παναγιώτης[EN] Verginis, Panayotis [EL] Μητρούλης, Ιωάννης[EN] Mitroulis, Ioannis [EL] Μπούμπας, Δημήτριος[EN] Boumpas, Dimitrios
Ημερομηνία:	28/11/2019
Περίληψη:	Objectives Haematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both myeloid and lymphoid cell lineages. We reasoned that the aberrancies of immune cells in systemic lupus erythematosus (SLE) could be traced back to HSPCs. Methods A global gene expression map of bone marrow (BM)-derived HSPCs was completed by RNA sequencing followed by pathway and enrichment analysis. The cell cycle status and apoptosis status of HSPCs were assessed by flow cytometry, while DNA damage was assessed via immunofluorescence. Results Transcriptomic analysis of Lin−Sca-1+c-Kit+ haematopoietic progenitors from diseased lupus mice demonstrated a strong myeloid signature with expanded frequencies of common myeloid progenitors (CMPs)—but not of common lymphoid progenitors—reminiscent of a ‘trained immunity’ signature. CMP profiling revealed an intense transcriptome reprogramming with suppression of granulocytic regulators indicative of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, and disturbed myelopoiesis. Despite the differentiation arrest, frequencies of BM neutrophils were markedly increased in diseased mice, suggesting an alternative granulopoiesis pathway. In patients with SLE with severe disease, haematopoietic progenitor cells (CD34+) demonstrated enhanced proliferation, cell differentiation and transcriptional activation of cytokines and chemokines that drive differentiation towards myelopoiesis, thus mirroring the murine data. Conclusions Aberrancies of immune cells in SLE can be traced back to the BM HSPCs. Priming of HSPCs and aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare.
Γλώσσα:	Αγγλικά
Σελίδες:	12
DOI:	10.1136/annrheumdis-2019-215782
ISSN:	0003-4967
Θεματική κατηγορία:	[EL] Ιατρική έρευνα και Πειραματική ιατρική[EN] Research and Experimental medicine
Κάτοχος πνευματικών δικαιωμάτων:	© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/.
Διατίθεται ανοιχτά στην τοποθεσία:	https://ard.bmj.com/content/79/2/242
Ηλεκτρονική διεύθυνση του τεκμηρίου στον εκδότη:	https://ard.bmj.com/content/79/2/242
Ηλεκτρονική διεύθυνση περιοδικού:	https://ard.bmj.com/
Τίτλος πηγής δημοσίευσης:	Annals of the Rheumatic Diseases (ARD)
Τεύχος:	2
Τόμος:	79
Σελίδες τεκμηρίου (στην πηγή):	242–253
Σημειώσεις:	This work was supported by a research grant from FOREUM Foundation for Research in Rheumatology, from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 742390). The research leading to these results has been cofunded by the European Commission under the H2020 Research Infrastructures contract no. 675121 (project VI-­SEEM). Computational time was granted from the VI-­SEEM project and the Greek National HPC facility—ARIS under project ID “RNA_LUPUS”. MG is financed by Greece and the European Union (European Social Fund) through the Operational Programme ’Human Resources Development, Education and Lifelong Learning’ in the context of the project ’Strengthening Human Resources Research Potential via Doctorate Research’ (MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ). MG is a PhD candidate at University of Athens. This work is submitted in fulfilment of the requirement for the PhD. AB is financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme ’Human Resources Development, Education and Lifelong Learning’ in the context of the project ’Reinforcement of Postdoctoral Researchers’ (MIS-5001552), implemented by the State Scholarships Foundation (ΙΚΥ).
Εμφανίζεται στις συλλογές:	Μεταδιδακτορικοί ερευνητές