Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

Hatada, Izuho; Morita, Sumiyo; Kimura, Masashi; Horii, Takuro; Yamashita, Riu; Nakai, Kenta

doi:10.1007/s10038-007-0228-0

Cited by 18 publications

(22 citation statements)

References 18 publications

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“…At the same times, also the methyl absorption band at 2873 cm −1 decreases in intensity. We believe that the changes in the 2936 cm −1 shoulder could reflect variations in the methylation levels of stem cell DNA and histones during differentiation [7,14]. This result, if confirmed by molecular biology assays on the examined ES cells, could be of particular relevance, considering the role played by the methyl groups dynamics in all the biological phenomena governed by epigenomic changes regulating gene expression.…”

Section: Ft-ir Response Of Differentiating Es Cells In the 3050-2800 supporting

confidence: 56%

FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation

et al. 2010

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Abstract.As recently pointed out in the literature, Fourier transform infrared (FT-IR) spectroscopy is emerging as a powerful tool in stem cell research. In this work we characterized in situ by FT-IR microspectroscopy the differentiation of murine embryonic stem cells (ES) to monitor possible changes in the cell macromolecular content during the early stages of differentiation. Undifferentiated and differentiating cells at 4, 7, 9 and 14 days were measured. Data were analyzed by the principal component and subsequent linear discriminant analyses (PCA-LDA) that enabled us to segregate ES cell spectra into well separate clusters and to identify the most significant spectral changes. Important changes in the lipid (3050-2800 cm −1 ), protein (1700-1600 cm −1 ) and in the nucleic acid (1050-850 cm −1 ) absorption regions were observed between days 4 to 7 of differentiation, indicating the appearance -at day 7 -of the new phenotype into cardiomyocyte precursors. Also the presence of DNA/RNA hybrid bands (954 cm −1 and 899 cm −1 ) suggests that the transcriptional switch of the genome started at this stage of differentiation. Particularly noteworthy, we suggest that the 2936 cm −1 shoulder we observed could reflect methyl group vibrations thus allowing the detection of variations in methylation levels of the stem cell during differentiation. These infrared results were found to be in agreement with the biochemical characterization of these differentiating cells, underlying the great potential of FT-IR spectroscopy in stem cell research.

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Section: Ft-ir Response Of Differentiating Es Cells In the 3050-2800 supporting

confidence: 56%

FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation

et al. 2010

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“…Hence, we scrutinized previously published microarray data [35] for proteases whose expression was upregulated upon differentiation of P19 cells. We focused on matrix metalloproteinases and extracellular serine proteases, since previous work suggested members of these families to be involved in Reelin processing [18], [34].…”

Section: Resultsmentioning

confidence: 99%

“…Adapted from Hatada and colleagues [35]. Analysis of the microarray data [35] yielded 19 serine proteases, 20 metalloproteinases, 4 convertases, and 10 proteinase inhibitors being up-regulated upon retinoic-acid induced differentiation of embryonic P19 tetracarcinoma cells into neurons.…”

Section: Supporting Informationmentioning

confidence: 99%

Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators

2012

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The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer's disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), α-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD.

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“…Thus, other mechanisms such as chromatin remodeling may also play a role in gene expression [246]. We know P19 cells treated with RA differentiate towards a neuronal lineage [49, 51], and this is marked by global demethylation [247], which is similar to what is seen in F9 cells treated with RA [239]. A reduction in DNMT protein levels and activity leads to reduced global and gene-specific methylation involved in differentiation seen in other ECCs [237, 239, 248, 249].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Kelly

Gatie

2017

Stem Cells International

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Just over ten years have passed since the seminal Takahashi-Yamanaka paper, and while most attention nowadays is on induced, embryonic, and cancer stem cells, much of the pioneering work arose from studies with embryonal carcinoma cells (ECCs) derived from teratocarcinomas. This original work was broad in scope, but eventually led the way for us to focus on the components involved in the gene regulation of stemness and differentiation. As the name implies, ECCs are malignant in nature, yet maintain the ability to differentiate into the 3 germ layers and extraembryonic tissues, as well as behave normally when reintroduced into a healthy blastocyst. Retinoic acid signaling has been thoroughly interrogated in ECCs, especially in the F9 and P19 murine cell models, and while we have touched on this aspect, this review purposely highlights how some key transcription factors regulate pluripotency and cell stemness prior to this signaling. Another major focus is on the epigenetic regulation of ECCs and stem cells, and, towards that end, this review closes on what we see as a new frontier in combating aging and human disease, namely, how cellular metabolism shapes the epigenetic landscape and hence the pluripotency of all stem cells.

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Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

Cited by 18 publications

References 18 publications

FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation

FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation

Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

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