Reprogramming fibroblasts to neural-precursor-like cells by structured overexpression of pallial patterning genes

Raciti, Marilena; Granzotto, Marilena; M, Duc; Fimiani, Cristina; Cellot, Giada; Cherubini, Enrico; Mallamaci, Antonello

doi:10.1016/j.mcn.2013.10.004

Cited by 25 publications

(19 citation statements)

References 74 publications

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“…Therefore we hypothesized histone methylation played a role in the T 3 -mediated regulation of viral replication and gene expression. To test the hypothesis, we performed the experiments using our in vitro differentiated cell culture reactivation model with trans -2-phenyl-Cyclopropylamine hydrochloride (TCP), a histone demethylase inhibitor (34). Under the treatment of TCP, the histones inside the cells remained hypermethylated.…”

Section: Resultsmentioning

confidence: 99%

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells

Figliozzi

Chen

Balish

et al. 2014

Journal of the Neurological Sciences

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A global HSV-1 gene repression occurs during latency in sensory neurons where most viral gene transcriptions are suppressed. The molecular mechanisms of gene silencing and how stress factors trigger the reactivation are not well understood. Thyroid hormones are known to be altered due to stress, and with its nuclear receptor impart transcriptional repression or activation depending upon the hormone level. Therefore we hypothesized that triiodothyronine (T3) treatment of infected differentiated neuron like cells would reduce the ability of HSV-1 to produce viral progeny compared to untreated infected cells. Previously we identified putative thyroid hormone receptor elements (TREs) within the promoter regions of HSV-1 thymidine kinase (TK) and other key genes. Searching for a human cell line that can model neuronal HSV-1 infection, we performed HSV-1 infection experiments on differentiated human neuroendocrine cells, LNCaP. Upon androgen deprivation these cells undergo complete differentiation and exhibit neuronal-like morphology and physiology. These cells were readily infected by our HSV-1 recombinant virus, expressing GFP and maintaining many processes iconic of dendritic morphology. Our results demonstrated that differentiated LNCaP cells produced suppressive effects on HSV-1 gene expression and replication compared to its undifferentiated counterpart and T3 treatment have further decreased the viral plaque counts compared to untreated cells. Upon washout of the T3 viral plaque counts were restored, indicating an increase of viral replication. The qRT-PCR experiments using primers for TK showed reduced expression under T3 treatment. ChIP assays using a panel of antibodies for H3 lysine 9 epigenetic marks showed increased repressive marks on the promoter regions of TK. In conclusion we have demonstrated a T3 mediated quiescent infection in differentiated LNCaP cells that has potential to mimic latent infection. In this HSV-1 infection model thyroid hormone treatment caused decreased viral replication, repressed TK expression and increased repressive histone tail marks on the TK promoter.

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Section: Resultsmentioning

confidence: 99%

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells

Figliozzi

Chen

Balish

et al. 2014

Journal of the Neurological Sciences

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“…In fact, both heterozygous FOXG1 duplication and deletion are associated with severe cognitive impairment, loss of speech, and developmental epilepsy 14, 15 . FOXG1 overexpression inhibits gliogenesis and promotes neurogenesis in Neural-Stem Cells (NSCs); in fact, it can reprogram fibroblasts into Neural-precursor-like cells when paired with PAX6 overexpression 16, 17 . On top of this, FoxG1 directly controls the levels of PAX6, another transcription factor equally important for promoting neural stem cell proliferation and inhibiting premature neuronal differentiation during early forebrain development 18-25 .…”

Section: Introductionmentioning

confidence: 99%

Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1+/− patients and in foxg1+/− mice

et al. 2015

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Rett Syndrome (RTT) is a severe neurodevelopmental disorder associated with mutations in either MECP2, CDKL5 or FOXG1. The precise molecular mechanisms that lead to the pathogenesis of RTT have yet to be elucidated. We recently reported that expression of GluD1 (orphan Glutamate receptor Delta-1 subunit) is increased in iPSC-derived neurons obtained from patients with mutations in either MECP2 or CDKL5. GluD1 controls synaptic differentiation and shifts the balance between excitatory and inhibitory synapses towards the latter. Thus, an increase in GluD1 might be a critical factor in the etiology of RTT by affecting the excitatory/inhibitory balance in the developing brain. To test this hypothesis, we generated iPSC-derived neurons from FOXG1+/− patients. We analyzed mRNA and protein levels of GluD1 together with key markers of excitatory and inhibitory synapses in these iPSC-derived neurons and in Foxg1+/− mouse fetal (E11.5) and adult (P70) brains. We found strong correlation between iPSC-derived neurons and fetal mouse brains, where GluD1 and inhibitory synaptic markers (GAD67 and GABA AR-α1) were increased, while the levels of a number of excitatory synaptic markers (VGLUT1, GluA1, GluN1, PSD-95) were decreased. In adult mice, GluD1 was decreased along with all GABAergic and glutamatergic markers. Our findings further the understanding of the etiology of RTT by introducing a new pathological event occurring in the brain of FOXG1+/− patients during embryonic development and its time-dependent shift toward a general decrease in brain synapses.

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“…The

c_{2} - c_{0}

branch is mediated by 39 transition genes including LHX2, FEZF2, FOXG1, HMGA1, SP8, OTX1, SOX11, GLI3, SIX3 , and ETV5 which suggest that

c_{2}

is comprised of cortical progenitors (Appolloni et al, 2008; Greig et al, 2013; Kishi et al, 2012; Manuel et al, 2011; Raciti et al, 2013). The

c_{0} - c_{3}

branch is mediated by 55 transition genes including GTF2I, HIF1A, ID1, ID3, PROX1, POU3F2, SALL1, SOX21 TCF12, TRPS1 and ZHX2 , which are associated with mesencephalon and metencephalon regional development, as well as having known involvement with midbrain/hindbrain organizer identity (Buck et al, 2001; Enkhmandakh et al, 2009; Inoue et al, 2012; Jaegle et al, 2003; Kunath et al, 2002; Lavado and Oliver, 2007; Milosevic et al, 2007; Ohba et al, 2004; Uittenbogaard and Chiaramello, 2002; Yao et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

Discovering sparse transcription factor codes for cell states and state transitions during development

Furchtgott

Melton

Menon

et al. 2017

eLife

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Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships. We use this technique to reconstruct the early hematopoietic and intestinal developmental trees. We extend this framework to analyze single-cell RNA-seq data from early human cortical development, inferring a neocortical-hindbrain split in early progenitor cells and the key genes that could control this lineage decision. Our work allows us to simultaneously infer both the identity and lineage of cell types as well as a small set of key genes whose expression patterns reflect these relationships.DOI: http://dx.doi.org/10.7554/eLife.20488.001

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Reprogramming fibroblasts to neural-precursor-like cells by structured overexpression of pallial patterning genes

Cited by 25 publications

References 74 publications

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells

Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1+/− patients and in foxg1+/− mice

Discovering sparse transcription factor codes for cell states and state transitions during development

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