Epigenetic Modifications in Distinction: Histone versus DNA Methylation in ESCs

In this issue of Cell Stem Cell, Karimi et al. (2011) show that DNA methylation and histone H3 lysine 9 trimethylation (H3K9me3) have distinct genomic targets in mouse ESCs. In particular, loss of H3K9me3 leads to derepression of select endogenous retroviruses and subsequent ectopic transcription of adjacent genes

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes.</p> <p>Results</p> <p>We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation.</p> <p>Conclusion</p> <p>Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology.</p

Impacts of Abnormal Heating of Tibetan Plateau on Rossby Wave Activity and Hazards Related to Snow and Ice in South China

In January 2008, extreme freezing rain struck South China. At the same time, the Tibetan Plateau (TP) was experiencing pronounced surface heating. The characteristics of this extreme weather and its linkage to the TP surface heating anomaly were analyzed in this paper. The results show that (1) anomalous heating of the TP helps to form and sustain the Siberian blocking high, which is important for persistent southward flow of dry and cold Siberian air; (2) TP heating helps the moisture flux move more north and strengthens the southerly wind above 850 hPa; (3) there are two Rossby wave trains at 500 hPa and the layers above it (at about 20∘N–40∘N). Correlation analysis reveals that TP heating anomalies are closely associated with these Rossby wave trains; (4) the Rossby wave propagates downstream from the TP to South China in the mid and high layers of the atmosphere when the TP changes swiftly from a heat sink to a heat source. This implies that anomalous heating of the TP may stimulate the Rossby wave train to propagate downward in midlatitudes