During development of the mammalian central nervous system (CNS), neurons and glial cells (astrocytes and oligodendrocytes) are generated from common neural precursor cells (NPCs). However, neurogenesis precedes gliogenesis, which normally commences at later stages of fetal telencephalic development. Astrocyte differentiation of mouse NPCs at embryonic day (E) 14.5 (relatively late gestation) is induced by activation of the transcription factor STAT3, whereas at E11.5 (mid-gestation) NPCs do not differentiate into astrocytes even when stimulated by STAT3-activating cytokines such as leukemia inhibitory factor (LIF). This can be explained in part by the fact that astrocyte-specific gene promoters are highly methylated in NPCs at E11.5, but other mechanisms are also likely to play a role. We therefore sought to identify genes involved in the inhibition of astrocyte differentiation of NPCs at midgestation. We first examined gene expression profiles in E11.5 and E14.5 NPCs, using Affymetrix GeneChip analysis, applying the Percellome method to normalize gene expression level. We then conducted in situ hybridization analysis for selected genes found to be highly expressed in NPCs at midgestation. Among these genes, we found that N-myc and high mobility group AT-hook 2 (Hmga2) were highly expressed in the E11.5 but not the E14.5 ventricular zone of mouse brain, where NPCs reside. Transduction of N-myc and Hmga2 by retroviruses into E14.5 NPCs, which normally differentiate into astrocytes in response to LIF, resulted in suppression of astrocyte differentiation. However, sustained expression of N-myc and Hmga2 in E11.5 NPCs failed to maintain the hypermethylated status of an astrocyte-specific gene promoter. Taken together, our data suggest that astrocyte differentiation of NPCs is regulated not only by DNA methylation but also by genes whose expression is controlled spatio-temporally during brain development.
Identification of genes that restrict astrocyte differentiation of midgestational neural precursor cells.
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View Samplescompare wild type and Batf-/- B cells activated for 0 1 or 2 days in vitro.
The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells.
Specimen part
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Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
Specimen part, Cell line
View SamplesCHARGE syndrome is a congenital disorder caused by mutations in Chromodomain Helicase DNA-binding domain 7 (CHD7) gene. We performed single cell RNA-seq analysis in CTRL and CHD7-knockdown lt-NES cells. Overall design: Single cell RNA-Seq profiling of control (shCTRL) and CHD7-knockdown (sh410 or sh411) cells.
Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
Specimen part, Cell line, Subject
View SamplesWe performed a microarray experiment to analyze the transcriptional profile of human iPSC-derived neural stem/progenitor cells to identify CHD7 target genes
Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
No sample metadata fields
View SamplesCHARGE syndrome is caused by heterozygous mutations in a chromatin remodeler CHD7 and characterized by a set of malformations historically postulated to arise from defects in the neural crest formation during embryogenesis. To better delineate neural crest defects in CHARGE syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients with typical syndrome manifestations, and characterized neural crest cells differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of genes associated with cell migration was altered in CHARGE iPSC-NCCs as compared to control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination, migration and motility in vitro, and their transplantation in ovo revealed overall defective migratory activity in the chick embryo. Altogether, our results support the historical inference that CHARGE syndrome patients have defects in neural crest migration and provide the first successful application of patient-derived iPSCs in modeling craniofacial disorders.
CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations.
No sample metadata fields
View SamplesMouse lung CD11c+ dendritic cells are composed of 2 major DC subsets, the CD103+CD11b-low/intermediate DC (CD103+ DC) and the CD11b-highCD103- DC (CD11b-high DC). These 2 subsets are functionally distinct. Comparison of their functions showed CD103+ DC
Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment
View SamplesIn murine large intestinal lamina propria, CX3CR1high resident Mfs possess anti-inflammatory properties and thereby support intestinal homeostasis. Unlike other tissue-resident Ms, transcription factors that regulate differentiation and function of CX3CR1high Ms in the large intestine are poorly understood. Thus, to identify transcription factors specifically expressed in CX3CR1high Ms among large intestinal lamina propria innate myeloid cells, we comprehensively analyzed the genes expression profiles in CX3CR1high Ms, CX3CR1- CD11b+ CD11c+ cells, CD11b- CD11chigh DCs, and CD11b+CD11c- cells.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part
View SamplesTo determine the functions of Spi-C in innate immune responses, we investigated the overall gene expression patterns in M-CSF-BMDMFs prepared from Spicflox/flox and Lyz2-cre; Spicflox/flox mice. M-CSF-BMDMFs were stimulated with or without LPS following heme treatment and used for RNA-seq analysis. Overall design: Control and Spic–/– BMDMF pretreated with 40 µM hemin for 18 h were stimulated with (designated 'CNT_4' and 'cKO_4', respectively) or without (designated 'CNT_0' and 'cKO_0', respectively) 100 ng/ml LPS for 4 h.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment, Subject
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