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dc.contributor.authorLovelace, Michael D
dc.contributor.authorGu, Ben J
dc.contributor.authorEamegdool, Steven S
dc.contributor.authorWeible, Michael W
dc.contributor.authorWiley, James S
dc.contributor.authorAllen, David G
dc.contributor.authorChan-Ling, Tailoi
dc.date.accessioned2019-03-26T05:33:07Z
dc.date.available2019-03-26T05:33:07Z
dc.date.issued2015
dc.identifier.issn1066-5099
dc.identifier.doi10.1002/stem.1864
dc.identifier.urihttp://hdl.handle.net/10072/101325
dc.description.abstractDuring early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68+ microglia and astrocytes mediate phagocytosis during target‐dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple‐marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live‐cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum‐free environment, doublecortin+ (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7highDCXlow hNPCs and P2X7highDCXhigh neuroblasts, derived from primary cultures of human fetal telencephalon, phagocytosed targets including latex beads, apoptotic ReNcells, and apoptotic hNPC/neuroblasts. Pretreatment of neuroblasts and hNPCs with 1 mM adenosine triphosphate (ATP), 100 µM OxATP (P2X7 antagonist), or siRNA knockdown of P2X7 inhibited phagocytosis of these targets. Our results show that P2X7 functions as a scavenger receptor under serum‐free conditions resembling those in early neurogenesis. This is the first demonstration that hNPCs and neuroblasts may participate in clearance of apoptotic corpses during pre target‐dependent neurogenesis and mediate phagocytosis using P2X7 as a scavenger receptor.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAlphaMed Press, Inc.
dc.relation.ispartofpagefrom526
dc.relation.ispartofpageto541
dc.relation.ispartofissue2
dc.relation.ispartofjournalStem Cells
dc.relation.ispartofvolume33
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchOther biological sciences not elsewhere classified
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode319999
dc.subject.fieldofresearchcode32
dc.titleP2X7 receptors mediate innate phagocytosis by human neural precursor cells and neuroblasts
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorWeible, Michael W.


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