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Fibroblast growth factor 2 regulates activity and gene expression of human postâ mitotic excitatory neurons
dc.contributor.authorGupta, Shweta
dc.contributor.authorM‐redmond, Tanya
dc.contributor.authorMeng, Fan
dc.contributor.authorTidball, Andrew
dc.contributor.authorAkil, Huda
dc.contributor.authorWatson, Stanley
dc.contributor.authorParent, Jack M.
dc.contributor.authorUhler, Michael
dc.date.accessioned2018-05-15T20:14:34Z
dc.date.available2019-07-01T14:52:17Zen
dc.date.issued2018-05
dc.identifier.citationGupta, Shweta; M‐redmond, Tanya ; Meng, Fan; Tidball, Andrew; Akil, Huda; Watson, Stanley; Parent, Jack M.; Uhler, Michael (2018). "Fibroblast growth factor 2 regulates activity and gene expression of human postâ mitotic excitatory neurons." Journal of Neurochemistry 145(3): 188-203.
dc.identifier.issn0022-3042
dc.identifier.issn1471-4159
dc.identifier.urihttps://hdl.handle.net/2027.42/143704
dc.description.abstractMany neuropsychiatric disorders are thought to result from subtle changes in neural circuit formation. We used human embryonic stem cells and induced pluripotent stem cells (hiPSCs) to model mature, postâ mitotic excitatory neurons and examine effects of fibroblast growth factor 2 (FGF2). FGF2 gene expression is known to be altered in brain regions of major depressive disorder (MDD) patients and FGF2 has antiâ depressive effects in animal models of depression. We generated stable inducible neurons (siNeurons) conditionally expressing human neurogeninâ 2 (NEUROG2) to generate a homogenous population of postâ mitotic excitatory neurons and study the functional as well as the transcriptional effects of FGF2. Upon induction of NEUROG2 with doxycycline, the vast majority of cells are postâ mitotic, and the gene expression profile recapitulates that of excitatory neurons within 6 days. Using hES cell lines that inducibly express NEUROG2 as well as GCaMP6f, we were able to characterize spontaneous calcium activity in these neurons and show that calcium transients increase in the presence of FGF2. The FGF2â responsive genes were determined by RNAâ Seq. FGF2â regulated genes previously identified in nonâ neuronal cell types were upâ regulated (EGR1, ETV4, SPRY4, and DUSP6) as a result of chronic FGF2 treatment of siNeurons. Novel neuronâ specific genes were also identified that may mediate FGF2â dependent increases in synaptic efficacy including NRXN3, SYT2, and GALR1. Since several of these genes have been implicated in MDD previously, these results will provide the basis for more mechanistic studies of the role of FGF2 in MDD.Alterations in fibroblast growth factor (FGF) signaling have been implicated in major depressive disorder (MDD). In this article, human stem cells are differentiated into glutamatergic neurons. FGF2 treatment of these neurons increases activity as determined using calcium imaging. RNAseq studies implicate a number of genes in this regulation of neuronal activity by FGF2 including SYT2, NRXN3, and GALR1.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherneurogeninâ 2
dc.subject.otherstem cells
dc.subject.otherFGF2
dc.subject.otherglutamatergic
dc.subject.otherneuronal
dc.titleFibroblast growth factor 2 regulates activity and gene expression of human postâ mitotic excitatory neurons
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelNeurosciences
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143704/1/jnc14255-sup-0001-SupInfo.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143704/2/jnc14255-sup-0002-TableS1-S2.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143704/3/jnc14255.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143704/4/jnc14255_am.pdf
dc.identifier.doi10.1111/jnc.14255
dc.identifier.sourceJournal of Neurochemistry
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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