Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs dif...

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Autores principales:	Ioannis Kokkinopoulos, Aggelos Banos, Maria Grigoriou, Anastasia Filia, Theodora Manolakou, Themis Alissafi, Nikolaos Malissovas, Ioannis Mitroulis, Panayotis Verginis, Dimitrios T. Boumpas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be4200f7863143aca00bce2f9e1e9ac9
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spelling	oai:doaj.org-article:be4200f7863143aca00bce2f9e1e9ac92021-12-02T18:49:28ZPatrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury10.1038/s41598-021-95224-y2045-2322https://doaj.org/article/be4200f7863143aca00bce2f9e1e9ac92021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95224-yhttps://doaj.org/toc/2045-2322Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs differ from bone-marrow HSPCs both in SLE and healthy individuals, and how they participate in peripheral tissue injury. By employing next-generation RNA sequencing, the transcriptomes of CD34+ HSPCs deriving from the bone marrow and those patrolling the bloodstream of both healthy and individuals with SLE were compared. Patrolling SLE and Healthy human HSPC kinetics were examined through their inoculation into humanised mice. Patrolling and bone-marrow HSPCs have distinct molecular signatures, while patrolling SLE HSPCs showed an enhanced extramedullary gene expression profile. Non-mobilised, SLE-derived circulating HSPCs demonstrated altered homing capacities. Xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. Circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Patrolling SLE CD34+ HSPCs are able to home at extramedullary sites such as the spleen and kidneys, potentially participating in peripheral tissue injury.Ioannis KokkinopoulosAggelos BanosMaria GrigoriouAnastasia FiliaTheodora ManolakouThemis AlissafiNikolaos MalissovasIoannis MitroulisPanayotis VerginisDimitrios T. BoumpasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ioannis Kokkinopoulos Aggelos Banos Maria Grigoriou Anastasia Filia Theodora Manolakou Themis Alissafi Nikolaos Malissovas Ioannis Mitroulis Panayotis Verginis Dimitrios T. Boumpas Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
description	Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs differ from bone-marrow HSPCs both in SLE and healthy individuals, and how they participate in peripheral tissue injury. By employing next-generation RNA sequencing, the transcriptomes of CD34+ HSPCs deriving from the bone marrow and those patrolling the bloodstream of both healthy and individuals with SLE were compared. Patrolling SLE and Healthy human HSPC kinetics were examined through their inoculation into humanised mice. Patrolling and bone-marrow HSPCs have distinct molecular signatures, while patrolling SLE HSPCs showed an enhanced extramedullary gene expression profile. Non-mobilised, SLE-derived circulating HSPCs demonstrated altered homing capacities. Xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. Circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Patrolling SLE CD34+ HSPCs are able to home at extramedullary sites such as the spleen and kidneys, potentially participating in peripheral tissue injury.
format	article
author	Ioannis Kokkinopoulos Aggelos Banos Maria Grigoriou Anastasia Filia Theodora Manolakou Themis Alissafi Nikolaos Malissovas Ioannis Mitroulis Panayotis Verginis Dimitrios T. Boumpas
author_facet	Ioannis Kokkinopoulos Aggelos Banos Maria Grigoriou Anastasia Filia Theodora Manolakou Themis Alissafi Nikolaos Malissovas Ioannis Mitroulis Panayotis Verginis Dimitrios T. Boumpas
author_sort	Ioannis Kokkinopoulos
title	Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
title_short	Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
title_full	Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
title_fullStr	Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
title_full_unstemmed	Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
title_sort	patrolling human sle haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/be4200f7863143aca00bce2f9e1e9ac9
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Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury

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