The development and analysis of a human forebrain organoid as a model of fragile X syndrome (FXS) is reported in Nature Neuroscience this week, shedding new light on the molecular, cellular, and electrophysiological abnormalities associated with the condition. FXS is a heritable intellectual disability caused by the loss of an RNA-binding protein called fragile X mental retardation protein (FMRP). In the study, a team led by Emory University researchers used patient-derived induced pluripotent stem cells to create FXS forebrain organoids, observing that the loss of FMRP led to dysregulated neurogenesis, neuronal maturation, and neuronal excitability. Bulk and single-cell transcriptome analyses, meantime, reveal that the loss of FMRP altered gene expression in a cell-type-specific manner. Other findings include a large number of human-specific mRNAs bound by FMRP, including one that contributed to the altered gene expression in the FXS organoids.
A genomic and epigenomic analysis of peritoneal metastases, a hallmark of incurable gastric cancer, is presented in Nature Cancer this week, uncovering a potential new therapeutic strategy for the malignancy. In the study, a research team led by investigators from Japan's National Cancer Center Research Institute performed whole-genome sequencing, RNA sequencing, chromatin immunoprecipitation followed by sequencing, and methylation analyses on malignant ascitic fluid samples and corresponding tumor cell lines from 98 patients. They find multiple molecular targets enriched in gastric cancer with peritoneal metastasis. The scientists also identify a subgroup of patients with an active transforming growth factor-beta circuit and for whom drugs targeting TEAD family proteins may overcome therapeutic resistance. GenomeWeb has more on this, here.