Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells
Zhang YW, Mess J, Aizarani N, Mishra P, Johnson C, Romero-Mulero MC, Rettkowski J, Schoenberger K, Obier N, Jaecklein K, Woessner NM, Lalioti ME, Velasco-Hernandez T, Sikora K, Waesch R, Lehnertz B, Sauvageau G, Manke T, Menendez P, Walter SG, Minguet S, Laurenti E, Guenther S, Gruen D, Cabezas-Wallscheid N (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 24
Pages Range: 1038-1048
Journal Issue: 7
DOI: 10.1038/s41556-022-00931-x
Abstract
Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape of highly purified human bone marrow HSCs displaying varying degrees of dormancy. We identify the orphan receptor GPRC5C, which enriches for dormant human HSCs. GPRC5C is also essential for HSC function, as demonstrated by genetic loss- and gain-of-function analyses. Through structural modelling and biochemical assays, we show that hyaluronic acid, a bone marrow extracellular matrix component, preserves dormancy through GPRC5C. We identify the hyaluronic acid–GPRC5C signalling axis controlling the state of dormancy in mouse and human HSCs.
Involved external institutions
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
University of Cambridge
United Kingdom (GB)
Universitat de Barcelona (UB) / University of Barcelona
Spain (ES)
Université de Montréal
Canada (CA)
BIOSS Centre for Biological Signalling Studies
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
University of Cambridge
United Kingdom (GB)
Universitat de Barcelona (UB) / University of Barcelona
Spain (ES)
Université de Montréal
Canada (CA)
BIOSS Centre for Biological Signalling Studies
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
How to cite
APA:
Zhang, Y.W., Mess, J., Aizarani, N., Mishra, P., Johnson, C., Romero-Mulero, M.C.,... Cabezas-Wallscheid, N. (2022). Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells. Nature Cell Biology, 24(7), 1038-1048. https://dx.doi.org/10.1038/s41556-022-00931-x
MLA:
Zhang, Yu Wei, et al. "Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells." Nature Cell Biology 24.7 (2022): 1038-1048.
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