Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells
Zhang, Yu Wei (University of Freiburg, Germany)
Mess, Julian (University of Freiburg, Germany)
Aizarani, Nadim (University of Freiburg, Germany)
Mishra, Pankaj (University of Freiburg, Germany)
Johnson, Carys (University of Cambridge, UK)
Romero-Mulero, Mari Carmen (University of Freiburg, Germany)
Rettkowski, Jasmin (University of Freiburg, Germany)
Schönberger, Katharina (University of Freiburg, Germany)
Obier, Nadine (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Jäcklein, Karin (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Woessner, Nadine M. (University of Freiburg, Germany)
Lalioti, Maria Eleni (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Velasco-Hernandez, Talia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sikora, Katarzyna (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Wäsch, Ralph (University of Freiburg, Germany)
Lehnertz, Bernhard (University of Montreal, Canada)
Sauvageau, Guy (University of Montreal, Canada)
Manke, Thomas (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Menendez, Pablo (Institució Catalana de Recerca i Estudis Avançats)
Walter, Sebastian Gottfried (University Hospital of Cologne, Germany)
Minguet, Susana (University of Freiburg, Germany)
Laurenti, Elisa (University of Cambridge, UK)
Günther, Stefan (University of Freiburg, Germany)
Grün, Dominic (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)
Cabezas-Wallscheid, Nina (Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany)

Date:	2022
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.
Grants:	European Commission 813091 European Commission 792923 Agencia Estatal de Investigación PID2019-108160RB-I00
Note:	Altres ajuts: The Behrens-Weise-Foundation, the German Research Foundation (DFG) under the German Excellence Strategy (CIBSS-EXC-2189, project ID 390939984), SFB1425 (Project #422681845), SFB992 (Project #192904750; B07), SFB1479 (P05); Wellcome-MRC Cambridge Stem Cell Institute (203151/Z/16/Z)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Nature Cell Biology, Vol. 24 Núm. 7 (july 2022) , p. 1038-1048, ISSN 1476-4679

DOI: 10.1038/s41556-022-00931-x
PMID: 35725769

33 p, 20.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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