Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation

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dc.citation.firstpage2584en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleCell Reportsen_US
dc.citation.lastpage2595en_US
dc.citation.volumeNumber17en_US
dc.contributor.authorMatatall, Katie A.en_US
dc.contributor.authorJeong, Miraen_US
dc.contributor.authorChen, Siyien_US
dc.contributor.authorSun, Deqiangen_US
dc.contributor.authorChen, Fengjuen_US
dc.contributor.authorMo, Qianxingen_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorKing, Katherine Y.en_US
dc.date.accessioned2017-05-22T17:16:48Zen_US
dc.date.available2017-05-22T17:16:48Zen_US
dc.date.issued2016en_US
dc.description.abstractChronic infections affect a third of the world’s population and can cause bone marrow suppression, a severe condition that increases mortality from infection. To uncover the basis for infection-associated bone marrow suppression, we conducted repeated infection of WT mice with Mycobacterium avium. After 4–6 months, mice became pancytopenic. Their hematopoietic stem and progenitor cells (HSPCs) were severely depleted and displayed interferon gamma (IFN-γ) signaling-dependent defects in self-renewal. There was no evidence of increased HSPC mobilization or apoptosis. However, consistent with known effects of IFN-γ, transcriptome analysis pointed toward increased myeloid differentiation of HSPCs and revealed the transcription factor Batf2 as a potential mediator of IFN-γ-induced HSPC differentiation. Gain- and loss-of-function studies uncovered a role for Batf2 in myeloid differentiation in both murine and human systems. We thus demonstrate that chronic infection can deplete HSPCs and identify BATF2 as a mediator of infection-induced HSPC terminal differentiation.en_US
dc.identifier.citationMatatall, Katie A., Jeong, Mira, Chen, Siyi, et al.. "Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation." <i>Cell Reports,</i> 17, no. 10 (2016) Cell Press: 2584-2595. https://doi.org/10.1016/j.celrep.2016.11.031.en_US
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2016.11.031en_US
dc.identifier.urihttps://hdl.handle.net/1911/94317en_US
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.rightsThis is an open access article under the CC BY-NC-ND license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subject.keywordhematopoietic stem cellen_US
dc.subject.keywordchronic infectionen_US
dc.subject.keywordpancytopeniaen_US
dc.subject.keywordbone marrow failureen_US
dc.subject.keywordinterferon gammaen_US
dc.subject.keywordterminal differentiationen_US
dc.titleChronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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