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Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells

MPG-Autoren

Zhang,  Yu Wei
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Mess,  Julian
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Aizarani,  Nadim
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Romero-Mulero,  Mari Carmen
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rettkowski,  Jasmin
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Schönberger,  Katharina
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Obier,  Nadine
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Jäcklein,  Karin
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lalioti,  Maria-Eleni
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sikora,  Katarzyna
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Manke,  Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grün,  Dominic
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Cabezas-Wallscheid,  Nina
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Externe Ressourcen

https://www.nature.com/articles/s41556-022-00931-x
(Verlagsversion)

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10.1038_s41556-022-00931-x.pdf
(Verlagsversion), 21MB

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Zitation

Zhang, Y. W., Mess, J., Aizarani, N., Mishra, P., Johnson, C., Romero-Mulero, M. C., et al. (2022). Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells. Nature Cell Biology, 24, 1038-1048. doi:10.1038/s41556-022-00931-x.


Zitierlink: https://hdl.handle.net/21.11116/0000-000A-AB7D-A
Zusammenfassung
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.