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PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm

ABSTRACT: PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm

PROVIDER: PRJNA526532 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8710330.fastq.gz	Fastqsanger.gz
	SRR8710370.fastq.gz	Fastqsanger.gz
	SRR8710380.fastq.gz	Fastqsanger.gz
	SRR8710331.fastq.gz	Fastqsanger.gz
	SRR8710371.fastq.gz	Fastqsanger.gz

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PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm.

Project description:PAX6 is essential for neural retina (NR) and forebrain development but how PAX6 instructs NR versus forebrain specification remains unknown. We found that the paired-less PAX6, PAX6D, is expressed in NR cells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells. hESCs deficient for PAX6D failed to enter NR specification. Induced expression of PAX6D but not PAX6A in a PAX6-null background restored the NR specification capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and non-retinal neural genes that are potential targets of PAX6D, including WNT8B. Inhibition of WNTs or knocking down of WNT8B restored the NR specification capacity of neuroepithelia with PAX6D knockout, whereas activation of WNTs blocked NR specification even when PAX6D was induced. Thus, PAX6D specifies neuroepithelia to NR cells via the regulation of WNT8B.

| S-EPMC7507545 | biostudies-literature

PAX6D Instructs Neural Retinal Specification from Human Embryonic Stem Cell-Derived Neuroectoderm

Project description:PAX6 is essential for neural retina (NR) and forebrain development but how PAX6 instructs NR versus forebrain specification remains unknown. We found that the paired-less PAX6, PAX6D, is expressed in NR cells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells. hESCs deficient for PAX6D failed to enter NR specification. Induced expression of PAX6D but not PAX6A in a PAX6-null background restored the NR specification capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and non-retinal neural genes that are potential targets of PAX6D, including WNT8B. Inhibition of WNTs or knocking down of WNT8B restored the NR specification capacity of neuroepithelia with PAX6D knockout whereas activation of WNTs blocked NR specification even when PAX6D was induced. Thus, PAX6D specifies neuroepithelia to NR cells via regulation of WNT8B.

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Gene expression in retinal cells from wildtype H9 human embryonic stem cells, PAX6 KO and PAX6D KO cell lines

Project description:PAX6 is essential for eye and forebrain development but how PAX6 instructs retinal versus neuroectoderm specification remains unknown. We found that the paired-less PAX6, PAX6D, is uniquely expressed in retinal cells during human eye development and along human embryonic stem cell (hESC) differentiation to retinal cells. HESCs with deletion of PAX6D failed to enter retinal differentiation. Induced expression of PAX6D but not PAX6A under the PAX6-null background restored the retinal differentiation capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and neural genes that are targets of PAX6D, including WNT8B. Inhibition of WNTs restored the retinal differentiation capacity of neuroepithelia with PAX6D knockout whereas activation of WNTs blocks retinal differentiation even when PAX6D is induced. Thus, PAX6D specifies neuroepithelia to retinal cells, partly via regulation of WNTs.

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PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm

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Activin/Nodal signaling supports retinal progenitor specification in a narrow time window during pluripotent stem cell differentiation to anterior neuroectoderm

Project description:In this study, we used chemically-defined media to induce the in vitro differentiation of mouse embryonic stem cells (ESCs) towards eye field fates. Inhibition of Wnt/ß-Catenin signalling was sufficient to drive ESCs to telencephalic, but not retinal fates. Instead, retinal progenitors could be generated from competent differentiating mouse and human ESCs by the activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Our results reveal insights into the mechanisms of eye field specification and open new avenues towards the generation of retinal progenitors for translational medicine.

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Primary cilium-autophagy-Nrf2 (PAN) axis links the cell cycle to neuroectoderm fate in human embryonic stem cells

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