Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis

Nguyen, Trieu Hai; Abidin, Belma Melda et Heinonen, Krista M. ORCID: https://orcid.org/0000-0002-2410-4432 (2022). Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis Stem Cell Reports , vol. 17 , nº 10. pp. 2303-2317. DOI: 10.1016/j.stemcr.2022.08.004.

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Résumé

Emergency hematopoiesis involves the activation of bone marrow hematopoietic stem/progenitor cells (HSPCs) in response to systemic inflammation by a combination of cell-autonomous and stroma-dependent signals and leads to their release from bone marrow and migration to periphery. We have previously shown that FZD6 plays a pivotal role in regulating HSPC expansion and long-term maintenance. Now we sought to better understand the underlying mechanisms. Using lipopolysaccharide (LPS)-induced emergency granulopoiesis as a model, we show that failed expansion was intrinsic to FZD6-deficient HSPCs but also required a FZD6-deficient environment. FZD6-deficient HSPCs became more strongly activated, but their mobilization to peripheral blood was impaired and they were more susceptible to inflammatory cell death, leading to enhanced release of pro-inflammatory cytokines in the marrow. These studies indicate that FZD6 has a protective effect in the bone marrow to prevent an overactive inflammatory response and further suggest that mobilization improves HSPC survival during bone marrow inflammation.

Type de document:	Article
Mots-clés libres:	WNT signaling; Emergency hematopoiesis; Frizzled-6; Hematopoietic stem cells; Lipopolysaccharide
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	19 juill. 2023 05:06
Dernière modification:	19 juill. 2023 05:06
URI:	https://espace.inrs.ca/id/eprint/13434

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