Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2

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dc.citation.articleNumber108530
dc.citation.issueNumber12
dc.citation.journalTitleCell Reports
dc.citation.volumeNumber33
dc.contributor.authorFlorez, Marcus A.
dc.contributor.authorMatatall, Katie A.
dc.contributor.authorJeong, Youngjae
dc.contributor.authorOrtinau, Laura
dc.contributor.authorShafer, Paul W.
dc.contributor.authorLynch, Anne M.
dc.contributor.authorJaksik, Roman
dc.contributor.authorKimmel, Marek
dc.contributor.authorPark, Dongsu
dc.contributor.authorKing, Katherine Y.
dc.date.accessioned2021-02-08T18:37:43Z
dc.date.available2021-02-08T18:37:43Z
dc.date.issued2020
dc.description.abstractDuring chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we find that IFNγ disrupts the normally close interaction between HSCs and CXCL12-abundant reticular (CAR) cells in the HSC niche. IFNγ stimulation increases expression of the cell surface protein BST2, which we find is required for IFNγ-dependent HSC relocalization and activation. IFNγ stimulation of HSCs increases their E-selectin binding by BST2 and homing to the bone marrow, which depends on E-selectin binding. Upon chronic infection, HSCs from mice lacking BST2 are more quiescent and more resistant to depletion than HSCs from wild-type mice. Overall, this study defines a critical mechanism by which IFNγ promotes niche relocalization and activation in response to inflammatory stimulation and identifies BST2 as a key regulator of HSC quiescence.
dc.identifier.citationFlorez, Marcus A., Matatall, Katie A., Jeong, Youngjae, et al.. "Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2." <i>Cell Reports,</i> 33, no. 12 (2020) Cell Press: https://doi.org/10.1016/j.celrep.2020.108530.
dc.identifier.digitalInterferonGamma
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2020.108530
dc.identifier.urihttps://hdl.handle.net/1911/109804
dc.language.isoeng
dc.publisherCell Press
dc.rightsThis is an open access article under the CC BY-NC-ND license
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keywordhematopoietic stem cell
dc.subject.keywordinfection
dc.subject.keywordinterferon gamma
dc.subject.keywordniche
dc.subject.keywordhoming
dc.subject.keywordBST2
dc.subject.keywordE-selectin
dc.subject.keywordinflammation
dc.titleInterferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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