Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage

Andoh-Noda, Tomoko; Akamatsu, Wado; Miyake, Kunio; Matsumoto, Takuya; Yamaguchi, Ryo; Sanosaka, Tsukasa; Okada, Yohei; Kobayashi, Tetsuro; Ohyama, Manabu; Nakashima, Kinichi; Kurosawa, Hiroshi; Kubota, Takeo; Okano, Hideyuki

doi:10.1186/s13041-015-0121-2

Cited by 80 publications

(74 citation statements)

References 54 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the neurodevelopmental literature, a global reduction in DNA methylation and MeCP2 levels might be expected to promote astrocyte differentiation, and possibly delay or decrease neurogenesis [72,89]. In this way, alcohol would be similar to DNMT inhibitor treatment, which is known to induce differentiation along the astrocyte lineage [87].…”

Section: Fasd and Dna Methylationmentioning

confidence: 99%

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

Gavin

Grayson

Varghese

et al. 2017

Genes

View full text Add to dashboard Cite

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD.

show abstract

Section: Fasd and Dna Methylationmentioning

confidence: 99%

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

Gavin

Grayson

Varghese

et al. 2017

Genes

View full text Add to dashboard Cite

show abstract

“…The current study provides mass spectrometry-based quantitative proteomic data, depth of about 7000 proteins, using an earlier developed iPSC-based models involving RTT patient cells and isogenic controls [24]. We showed that changes in dendrite morphology or synaptic defects, previously associated with RTT [22, 32], already become apparent at early developmental stages. Proteins involved in immunity and metabolism, also in line with previous studies on RTT pathology [33, 34], are differentially expressed at all time points.…”

Section: Discussionmentioning

confidence: 87%

“…Here we used an iPSC-based RTT model and performed proteome analysis on iPSC-derived neuronal stem cells (NES cells) [21]. Earlier studies proved that iPSCs from RTT patients reflect disease-specific characteristics, including changes in neuronal differentiation at early stages of development [22, 23]. However, we lack knowledge on the precise molecular mechanisms underlying the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome

Varderidou-Minasian

Hinz

Hagemans

et al. 2019

Preprint

View full text Add to dashboard Cite

Rett syndrome (RTT) is a progressive neurodevelopmental disease often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanisms by which impaired MeCP2 induces the pathological abnormalities in the brain are not understood. To understand the molecular mechanisms involved in disease, we used an RTT patient induced pluripotent stem cell (iPSC)-based model and applied an in-depth high-resolution quantitative mass spectrometry-based analysis during early stages of neuronal development. Our data provide evidence of proteomic alteration at developmental stages long before the phase that symptoms of RTT syndrome become apparent. Differences in expression profiles became more pronounced from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes and calcium signaling were already affected at initial stages. These results can help development of new biomarkers and therapeutic approaches by selectively target the affected proteins in RTT syndrome.

show abstract

“…Furthermore, restoration of MeCP2 in the mutant astrocytes exerted a non-cell autonomous positive effect on mutant neurons in vivo, restoring dendritic morphology and increasing levels of the VGLUT1 transporter (Lioy et al 2011). Finally, it has been shown that Mecp2 is involved the differentiation of neural progenitors into astrocytes (Andoh-Noda et al 2015). These data showed that glia, like neurons, are integral components of the neuropathology of RTT.…”

Section: Introductionmentioning

confidence: 93%

Astrocyte Transcriptome from the Mecp2308-Truncated Mouse Model of Rett Syndrome

et al. 2015

View full text Add to dashboard Cite

Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome which is one of the most frequent sources of intellectual disability in women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett-like symptoms and restoration of Mecp2 can rescue some of these defects. The goal of this work is to compare gene expression profiles of wild-type and mutant astrocytes from Mecp2(308/y) mice (B6.129S-MeCP2/J) by using Affymetrix mouse 2.0 microarrays. Results were confirmed by quantitative real-time RT-PCR and by Western blot analysis. Gene set enrichment analysis utilizing Ingenuity Pathways was employed to identify pathways disrupted by Mecp2 deficiency. A total of 2152 genes were statistically differentially expressed between wild-type and mutated samples, including 1784 coding transcripts. However, only 257 showed fold changes >1.2. We confirmed our data by replicative studies in independent primary cultures of cortical astrocytes from Mecp2-deficient mice. Interestingly, two genes known to encode secreted proteins, chromogranin B and lipocalin-2, showed significant dysregulation. These proteins secreted from Mecp2-deficient glia may exert negative non-cell autonomous effects on neuronal properties, including dendritic morphology. Moreover, transcriptional profiling revealed altered Nr2f2 expression which may explain down- and upregulation of several target genes in astrocytes such as Ccl2, Lcn2 and Chgb. Unraveling Nr2f2 involvement in Mecp2-deficient astrocytes could pave the way for a better understanding of Rett syndrome pathophysiology and offers new therapeutic perspectives.

show abstract

Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage

Cited by 80 publications

References 54 publications

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome

Astrocyte Transcriptome from the Mecp2308-Truncated Mouse Model of Rett Syndrome

Contact Info

Product

Resources

About