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Mapping origins of variation in neural trajectories of human pluripotent stem cells [SOX21 KO RNA-seq]

ABSTRACT: Mapping origins of variation in neural trajectories of human pluripotent stem cells [SOX21 KO RNA-seq]

PROVIDER: PRJNA688714 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13331119_1.fastq.gz	Fastqsanger.gz
	SRR13331119_2.fastq.gz	Fastqsanger.gz
	SRR13331120_1.fastq.gz	Fastqsanger.gz
	SRR13331120_2.fastq.gz	Fastqsanger.gz
	SRR13331121_1.fastq.gz	Fastqsanger.gz

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Mapping origins of variation in neural trajectories of human pluripotent stem cells [SOX21 KO RNA-seq]

Project description:Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. We identify differences in the spontaneous self-organization of individual hPSC lines during self-renewal that lie along a fundamental axis of in vivo development. Distinct stable and dynamic transcriptional elements were revealed by decomposition of RNA-seq data in pluripotency and early lineage emergence. Stable differences within pluripotency predicted regional bias in the dynamics of neural differentiation that were also observed in large collections of hPSC lines. Using replicate human induced PSC (hiPSC) lines and paired adult tissue, we demonstrate that cells from individual humans expressed unique transcriptional signatures that were maintained throughout life. In addition, replicate hiPSC lines from one donor showed divergent expression phenotypes driven by distinct chromatin states. These stable transcriptional states are under both genetic and epigenetic control and predict bias in subsequent forebrain and hindbrain neural trajectories. These results define mechanisms controlling transcription in pluripotency to first establish human neural diversity.

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Mapping origins of variation in neural trajectories of human pluripotent stem cells

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Mapping origins of variation in neural trajectories of human pluripotent stem cells [RNA-seq]

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Mapping origins of variation in neural trajectories of human pluripotent stem cells

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

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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.

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

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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

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