ADRA1A-Gα signalling potentiates adipocyte thermogenesis through CKB and TNAP.

Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis. Aside from cAMP signalling downstream of β-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α-adrenergic receptor (AR) and β-AR signalling induces the expression of thermogenic genes of the futile creatine cycle, and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo.

Mapping Chromatin Accessibility in Human Naïve Pluripotent Stem Cells Using ATAC-Seq.

Regulatory elements, such as promoters and enhancers, typically show reduced nucleosome occupancy, which is a feature that is commonly referred to as "open chromatin". The distribution of open chromatin sites can provide important clues about the transcription factors and regulatory networks that drive gene expression in a given cell. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a rapid and robust method for mapping open chromatin sites.

Deletion of RBMX RGG/RG motif in Shashi-XLID syndrome leads to aberrant p53 activation and neuronal differentiation defects.

RNA-binding proteins play important roles in X-linked intellectual disability (XLID). In this study, we investigate the contribution of the XLID-associated RBMX in neuronal differentiation. We show that RBMX-depleted cells exhibit aberrant activation of the p53 pathway.

Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents.

Subcortical white matter stroke (WMS) accounts for up to 30% of all stroke events. WMS damages primarily astrocytes, axons, oligodendrocytes, and myelin. We hypothesized that a therapeutic intervention targeting astrocytes would be ideally suited for brain repair after WMS.

Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome.

Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting "transdifferentiated" hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts.

Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.

To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence.

A small molecule screen to identify regulators of let-7 targets.

The let-7 family of miRNAs has been shown to be crucial in many aspects of biology, from the regulation of developmental timing to cancer. The available methods to regulate this family of miRNAs have so far been mostly genetic and therefore not easily performed experimentally. Here, we describe a small molecule screen designed to identify regulators of let-7 targets in human cells.

Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R.

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain.

Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold.

Identifying gene expression modules that define human cell fates.

Using a compendium of cell-state-specific gene expression data, we identified genes that uniquely define cell states, including those thought to represent various developmental stages. Our analysis sheds light on human cell fate through the identification of core genes that are altered over several developmental milestones, and across regional specification. Here we present cell-type specific gene expression data for 17 distinct cell states and demonstrate that these modules of genes can in fact define cell fate.

Defining the role of oxygen tension in human neural progenitor fate.

Hypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells.

A host beetle pheromone regulates development and behavior in the nematode Pristionchus pacificus.

Nematodes and insects are the two most speciose animal phyla and nematode-insect associations encompass widespread biological interactions. To dissect the chemical signals and the genes mediating this association, we investigated the effect of an oriental beetle sex pheromone on the development and behavior of the nematode Pristionchus pacificus. We found that while the beetle pheromone is attractive to P.

let-7 miRNAs can act through notch to regulate human gliogenesis.

It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2.

RNAi mediated gene knockdown and transgenesis by microinjection in the necromenic Nematode Pristionchus pacificus.

Although it is increasingly affordable for emerging model organisms to obtain completely sequenced genomes, further in-depth gene function and expression analyses by RNA interference and stable transgenesis remain limited in many species due to the particular anatomy and molecular cellular biology of the organism. For example, outside of the crown group Caenorhabditis that includes Caenorhabditis elegans, stably transmitted transgenic lines in non-Caenorhabditis species have not been reported in this specious phylum (Nematoda), with the exception of Strongyloides stercoralis and Pristionchus pacificus. To facilitate the expanding role of P.