Zhang, Yu Wei ORCID: 0000-0002-6415-694X, Mess, Julian, Aizarani, Nadim, Mishra, Pankaj, Johnson, Carys, Romero-Mulero, Mari Carmen ORCID: 0000-0002-6705-7613, Rettkowski, Jasmin, Schoenberger, Katharina, Obier, Nadine, Jaecklein, Karin, Woessner, Nadine M., Lalioti, Maria-Eleni, Velasco-Hernandez, Talia ORCID: 0000-0003-2183-7443, Sikora, Katarzyna, Waesch, Ralph, Lehnertz, Bernhard, Sauvageau, Guy, Manke, Thomas, Menendez, Pablo, Walter, Sebastian Gottfried, Minguet, Susana, Laurenti, Elisa, Guenther, Stefan, Gruen, Dominic and Cabezas-Wallscheid, Nina (2022). Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells. Nat. Cell Biol., 24 (7). S. 1038 - 1071. BERLIN: NATURE PORTFOLIO. ISSN 1476-4679

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zhang, Yu WeiUNSPECIFIEDorcid.org/0000-0002-6415-694XUNSPECIFIED
Mess, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aizarani, NadimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mishra, PankajUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, CarysUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero-Mulero, Mari CarmenUNSPECIFIEDorcid.org/0000-0002-6705-7613UNSPECIFIED
Rettkowski, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenberger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obier, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaecklein, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woessner, Nadine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lalioti, Maria-EleniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velasco-Hernandez, TaliaUNSPECIFIEDorcid.org/0000-0003-2183-7443UNSPECIFIED
Sikora, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waesch, RalphUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehnertz, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sauvageau, GuyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manke, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menendez, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, Sebastian GottfriedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minguet, SusanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laurenti, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruen, DominicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabezas-Wallscheid, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-693572
DOI: 10.1038/s41556-022-00931-x
Journal or Publication Title: Nat. Cell Biol.
Volume: 24
Number: 7
Page Range: S. 1038 - 1071
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 1476-4679
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BINDING MOTIF; RECEPTOR; PEPTIDE; PROTEIN; EXPRESSION; PROGENITORS; GENES; CD44; ACID; EXITMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69357

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