Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner

Bibliographic Details
Title: Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
Authors: Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Source: Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract Hematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-41691-y
Access URL: https://doaj.org/article/45c592524cf44d3ebb3a8722a44142e6
Accession Number: edsdoj.45c592524cf44d3ebb3a8722a44142e6
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-41691-y
Published in:Nature Communications
Language:English