Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of Forkhead Box P1, in human iPSC-derived forebrain organoids with and without FOXP1. We generated cell type-specific gene expression profiles of FOXP1 in progenitors and excitatory neurons of dorsal telencephalic lineage.
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis. FACS isolated BPs at E13 and E16 mouse brain cortex were used for microarray analyses. Six biological replicates (embryonic cortex from three different litters) for E13 and five biological replicates (embryonic cortex from three different litters) for E16 were analysed.
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined miRNA expression profiles using mouse miRNA microarray (Agilent).Comparison of E13 and E16 microRNA expression profiles allowed us to identify regulatory mechanisms for maintaining stage specific homeostasis of BPs. FACS isolated BPs at E13 and E16 mouse brain cortex were used for miRNA microarray analyses. Four biological replicates (embryonic cortex from three different litters) for each group (E13 or E16) were analysed.
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis.
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined miRNA expression profiles using mouse miRNA microarray (Agilent).Comparison of E13 and E16 microRNA expression profiles allowed us to identify regulatory mechanisms for maintaining stage specific homeostasis of BPs.
Project description:Postnatal brain neurogenesis in mammals is believed to be restricted to rare germinative remnants of the neuroepithelium. In this study, we discovered that, in the postnatal brain, a subset of embryonically derived progenitors is present in meningeal substructures. These cells migrate from the meningeal substructures to the retrosplenial and visual motor cortex and differentiate into (electrically) functional integrated neurons. Lineage tracing analysis revealed that this subset of neural progenitors originate largely from PDGFR+ cells. PDGFR-derived cells differentiate mostly into Satb2+ neurons in cortical layers I-IV. Thus, a reservoir of embryonically derived progenitors in the meninges contributes to postnatal cerebral cortical neurogenesis.
Project description:Long-lived quiescent mammary stem cells (MaSCs) are presumed to coordinate the dramatic expansion of ductal epithelium that occurs through the different phases of postnatal development, but little is known about the molecular regulators that underpin the activation of MaSCs. Here we show that ablation of the transcription factor Foxp1 in the mammary gland profoundly impairs ductal morphogenesis, resulting in a rudimentary tree throughout adult life. Foxp1-deficient glands were highly enriched for quiescent Tspan8hi MaSCs, which failed to become activated, even in competitive transplantation assays, and therefore harbor a cell-intrinsic defect. Luminal cells aberrantly expressed basal genes, suggesting that Foxp1 may also contribute to cell-fate decisions. Notably, Foxp1 was uncovered as a direct repressor of the Tspan8 gene in basal cells and deletion of Tspan8 could rescue the profound defects in ductal morphogenesis elicited by Foxp1 loss. Thus, a single transcriptional regulator, Foxp1, can control the exit of MaSCs from dormancy to orchestrate differentiation and development.
Project description:Long-lived quiescent mammary stem cells (MaSCs) are presumed to coordinate the dramatic expansion of ductal epithelium that occurs through the different phases of postnatal development, but little is known about the molecular regulators that underpin the activation of MaSCs. Here we show that ablation of the transcription factor Foxp1 in the mammary gland profoundly impairs ductal morphogenesis, resulting in a rudimentary tree throughout adult life. Foxp1-deficient glands were highly enriched for quiescent Tspan8hi MaSCs, which failed to become activated, even in competitive transplantation assays, and therefore harbor a cell-intrinsic defect. Luminal cells aberrantly expressed basal genes, suggesting that Foxp1 may also contribute to cell-fate decisions. Notably, Foxp1 was uncovered as a direct repressor of the Tspan8 gene in basal cells and deletion of Tspan8 could rescue the profound defects in ductal morphogenesis elicited by Foxp1 loss. Thus, a single transcriptional regulator, Foxp1, can control the exit of MaSCs from dormancy to orchestrate differentiation and development.
Project description:To investigate the function of Foxp1 in the regulation of radial glial differentiation, we established Foxp1flox/flox;Emx1Cre mouse line in which Foxp1 is removed in cortical radial glia. We then performed gene expression profiling analysis using data obtained from bulk RNA-seq of 4 Cre negative controls and 2 mutants at E12.5.