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Updated: Nov 18, 2025

Streamlined 3D Cerebellar Differentiation Protocol with Optional 2D Modification

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Published on: December 9, 2017

PAUPAR and PAX6 sequentially regulate human embryonic stem cell cortical differentiation.

Yanxin Xu¹, Jiajie Xi¹, Guiying Wang¹

¹Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Nucleic Acids Research

|February 5, 2021

Summary

Long noncoding RNA (lncRNA) PAUPAR is essential for human cortical development. It interacts with PAX6 to epigenetically regulate neural gene expression during stem cell differentiation.

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Area of Science:

Developmental biology
Epigenetics
Neuroscience

Background:

Long noncoding RNAs (lncRNAs) are implicated in epigenetic regulation.
The role of lncRNAs in cortical development remains largely unknown.

Purpose of the Study:

To investigate the function of lncRNAs in human cortical development.
To identify novel regulators of human embryonic stem cell (hESC) differentiation.

Main Methods:

Utilized hESC-based 2D neural differentiation and 3D cerebral organoid models.
Investigated the lncRNA PAUPAR and its interaction with the transcription factor PAX6.
Performed mechanistic studies on gene regulation and epigenetic modifications.

Main Results:

Identified lncRNA PAUPAR as crucial for cortical differentiation.
PAUPAR interacts with PAX6 to regulate numerous neural genes.
PAUPAR facilitates PAX6 binding to target genes and recruits NSD1 for H3K36 methylation.

Conclusions:

The PAUPAR/PAX6/NSD1 complex is critical for epigenetic regulation during hESC cortical differentiation.
PAUPAR is an intrinsic regulator of cortical development.