Publication

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease caused by degeneration of motor neurons leading to rapidly progressive paralysis. About 10% of cases are caused by gain-of-function mutations that are transmitted as dominant traits. A potential therapy for these cases is to suppress the expression of the mutant gene.

Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking.

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (gamma-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas.

Although additional sex combs-like 1 (ASXL1) has been extensively described in hematologic malignancies, little is known about the molecular role of ASXL1 in organ development. Here, we show that Asxl1 ablation in mice results in postnatal lethality due to cyanosis, a respiratory failure. This lung defect is likely caused by higher proliferative potential and reduced expression of surfactant proteins, leading to reduced air space and defective lung maturation. By microarray analysis, we identified E2F1-responsive genes, including Nmyc, as targets repressed by Asxl1.

Recently three different cyclin-dependent kinase 4 and 6 (CDK4/6) dual inhibitors were approved for the treatment of breast cancer (palbociclib, ribociclib and abemaciclib), all of which offer comparable therapeutic benefits. Their safety profiles however are different.

The factors responsible for the low detection rate of cell-free tumor DNA (ctDNA) in the plasma of glioblastoma (GB) patients are currently unknown. In this study, we measured circulating nucleic acids in patient-derived orthotopically implanted xenograft (PDOX) models of GB (n=64) and show that tumor size and cell proliferation, but not the integrity of the blood-brain barrier or cell death, affect the release of ctDNA in treatment naïve GB PDOX.

T cells in colorectal cancer (CRC) are associated with improved survival. However, checkpoint immunotherapies antagonizing the suppression of these cells are ineffective in the great majority of patients. To better understand the immune cell regulation in CRC, we compared tumor-associated T lymphocytes and macrophages to the immune cell infiltrate of normal mucosa. Human colorectal tumor specimen and tumor-distant normal mucosa tissues of the same patients were collected.

Epithelial-neuronal signaling is essential for sensory encoding in touch, itch, and nociception; however, little is known about the release mechanisms and neurotransmitterreceptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission.

Oestrogen receptor α (ERα) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERα-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERα-negative responder cells.

Excess caloric intake results in increased fat accumulation and an increase in energy expenditure via diet-induced adaptive thermogenesis; however, the underlying mechanisms controlling these processes are unclear.