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SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

ABSTRACT: SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

PROVIDER: PRJNA433877 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6713240.fastq.gz	Fastqsanger.gz
	SRR6713241_1.fastq.gz	Fastqsanger.gz
	SRR6713241_2.fastq.gz	Fastqsanger.gz
	SRR6713242_1.fastq.gz	Fastqsanger.gz
	SRR6713242_2.fastq.gz	Fastqsanger.gz

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SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

Project description:SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

| PRJNA433872 | ENA

SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

Project description:SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

| PRJNA574589 | ENA

SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

Project description:Generation of brain region-specific progenitors from human embryonic stem cells (hESCs) is critical for their application. However, transcriptional regulation of neural regionalization in human embryos is poorly understood. Here, we report that transcription factor SOX21 is required for telencephalic fate specification from hESCs. SOX21 knockout (KO) impairs telencephalic fate specification, concomitant with the activation of diencephalic genes and Wnt signaling. Inhibition of Wnt signaling restores telencephalic specification from SOX21 KO hESCs. Analysis of global SOX21 DNA binding profiles and SOX21-regulated genes identifies SOX21 targets. SOX21 interacts with b-catenin and interferes with TCF4/b-catenin binding to the enhancer of WNT8B. Double KO of SOX21 and WNT8B restores telencephalic specification, indicating that SOX21 specifies the telencephalic fate through repressing WNT8B expression. Moreover, the high and low levels of SOX21 in the telencephalon and diencephalon, respectively, in developing human brains support its role in telencephalic fate specification. Collectively, this study unveils previously unappreciated roles of SOX21 and sheds light on the transcriptional control of telencephalic patterning in humans.

2019-10-28 | GSE138094 | GEO

SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

2019-10-28 | GSE110504 | GEO

SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells.

Project description:The generation of brain region-specific progenitors from human embryonic stem cells (hESCs) is critical for their application. However, transcriptional regulation of neural regionalization in humans is poorly understood. Here, we applied a rostrocaudal patterning system from hESCs to dissect global transcriptional networks controlling early neural regionalization. We found that SOX21 is required for rostral forebrain fate specification. SOX21 knockout led to activation of Wnt signaling, resulting in caudalization of regional identity of rostral forebrain neural progenitor cells. Moreover, we identified WNT8B as a SOX21 direct target. Deletion of WNT8B or inhibition of Wnt signaling in SOX21 knockout neural progenitor cells restored rostral forebrain identity. Furthermore, SOX21 interacted with β-catenin, interfering with the binding of TCF4/β-catenin complex to the WNT8B enhancer. Collectively, these results unveil the unknown role of SOX21 and shed light on how a transcriptional factor modulates early neural regionalization through crosstalk with a key component of Wnt signaling.

| S-EPMC6915843 | biostudies-literature

SOX21 ensures rostral forebrain identity by suppression of WNT8B during neural regionalization of human embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-10-28 | GSE110506 | GEO

SOX1 is required for the specification of rostral hindbrain neural progenitor cells from human embryonic stem cells

Project description:Region-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) through modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization are not well characterized. Here, we generate region-specific NPCs from hESCs and find that SOX1 is highly expressed in NPCs with the rostral hindbrain identity. Moreover, we find that OTX2 inhibits SOX1 expression, displaying exclusive expression between the two factors. Furthermore, SOX1 knockout (KO) leads to up-regulation of midbrain genes and down-regulation of rostral hindbrain genes, indicating that SOX1 is necessary for specification of rostral hindbrain NPCs. Our SOX1 ChIP-sequencing analysis reveals that SOX1 binds to the distal region of GBX2 to activate its expression. Overexpression of GBX2 largely abrogates SOX1-KO induced aberrant gene expression. Taken together, this study uncovers previously unappreciated role of SOX1 in early neural regionalization and provides new information for the precise control of the OTX2/GBX2 interface.

2020-08-26 | GSE138218 | GEO

Expression data from rostral forebrains of wild-type and Fezf1-/- Fezf2-/- mice

Project description:Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon. We compared gene expression profiles of rostral forebrains, which contain the telencephalon and the rostral part of the diencephalon, from embryonic day (E) 9.5, E10.5, and E12.5 wild-type control and Fezf1-/- Fezf2 -/- mouse embryos. The forebrain rostral to the caudal limit of the lateral ventricles was isolated manually from E9.5, E10.5, and E12.5 wild-type and Fezf1-/- Fezf2-/- mice. Total RNAs were isolated by Separsol-RNA I and were used for microarray analyses.

2010-04-12 | E-GEOD-21156 | biostudies-arrayexpress

Genome-wide map of SOX21 occupancy in human embryonic stem cell-derived neural progenitor cells [ChIP-seq]

Project description:To understand how SOX21 regulates neural fate specification, we differentiated wild type and SOX21 knockout hESC into neural epithelial cells (NECs) using dual SMAD inhibition protocol. We collected cells at neural differentiation day 5 and performed SOX21 ChIP-seq to investigate the genome-wide binding profiles. Meanwhile, we also carried out b-catenin ChIP-seq in wild type and SOX21 knockout NECs to dissect the role of SOX21 in Wnt signaling inhibition, thus providing important information for the mechanism underlying SOX21's functions in early neural fate specification.

2019-10-28 | GSE110505 | GEO

Expression data from E12.5 ePet-EYFP rostral and caudal serotonin (5HT) neurons purified by flow cytometry

Project description:The 5HT system is organized into rostral and caudal populations with discrete anatomical locations and opposite axonal trajectories in the developing hindbrain. 5HT neuron cell bodies in the rostral subdivision migrate to the midbrain and pons and extend ascending projections throughout the forebrain. 5HT cell bodies in the caudal subdivision migrate to the ventral medulla and caudal half of the pons and provide descending projections to the brainstem and spinal cord.

2009-12-16 | GSE19474 | GEO

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