» Articles » PMID: 20621053

Pax6 is a Human Neuroectoderm Cell Fate Determinant

Overview
Journal Cell Stem Cell
Publisher Cell Press
Specialty Cell Biology
Date 2010 Jul 13
PMID 20621053
Citations 250
Authors
Affiliations
Soon will be listed here.
Abstract

The transcriptional regulation of neuroectoderm (NE) specification is unknown. Here we show that Pax6 is uniformly expressed in early NE cells of human fetuses and those differentiated from human embryonic stem cells (hESCs). This is in contrast to the later expression of Pax6 in restricted mouse brain regions. Knockdown of Pax6 blocks NE specification from hESCs. Overexpression of either Pax6a or Pax6b, but not Pax6triangle upPD, triggers hESC differentiation. However, only Pax6a converts hESCs to NE. In contrast, neither loss nor gain of function of Pax6 affects mouse NE specification. Both Pax6a and Pax6b bind to pluripotent gene promoters but only Pax6a binds to NE genes during human NE specification. These findings indicate that Pax6 is a transcriptional determinant of the human NE and suggest that Pax6a and Pax6b coordinate with each other in determining the transition from pluripotency to the NE fate in human by differentially targeting pluripotent and NE genes.

Citing Articles

PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells.

Guo X, Wang L, Zheng F, Li H Heliyon. 2025; 11(2):e41795.

PMID: 39885876 PMC: 11780942. DOI: 10.1016/j.heliyon.2025.e41795.


A Comprehensive Functional Investigation of the Human Translocator Protein 18 kDa (TSPO) in a Novel Human Neuronal Cell Knockout Model.

Bader S, Jahner T, Dorfelt A, Melchner D, Cardon I, Siegmund H Int J Mol Sci. 2024; 25(23).

PMID: 39684592 PMC: 11641651. DOI: 10.3390/ijms252312882.


Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures.

Popp J, Rhodes K, Jangi R, Li M, Barr K, Tayeb K Cell Genom. 2024; 4(12):100701.

PMID: 39626676 PMC: 11701260. DOI: 10.1016/j.xgen.2024.100701.


Lactate promotes H3K18 lactylation in human neuroectoderm differentiation.

Wu Y, Wang Y, Dong Y, Sun L, Zheng Y Cell Mol Life Sci. 2024; 81(1):459.

PMID: 39562370 PMC: 11576721. DOI: 10.1007/s00018-024-05510-x.


NMNAT1 Is Essential for Human iPS Cell Differentiation to the Retinal Lineage.

Kuribayashi H, Iwagawa T, Murakami A, Kawamura T, Suzuki Y, Watanabe S Invest Ophthalmol Vis Sci. 2024; 65(12):37.

PMID: 39446354 PMC: 11512567. DOI: 10.1167/iovs.65.12.37.


References
1.
Mizuseki K, Kishi M, Matsui M, Nakanishi S, Sasai Y . Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. Development. 1998; 125(4):579-87. DOI: 10.1242/dev.125.4.579. View

2.
Fong H, Hohenstein K, Donovan P . Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells. 2008; 26(8):1931-8. DOI: 10.1634/stemcells.2007-1002. View

3.
Matin M, Walsh J, Gokhale P, Draper J, Bahrami A, Morton I . Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells. 2004; 22(5):659-68. DOI: 10.1634/stemcells.22-5-659. View

4.
Kroon E, Martinson L, Kadoya K, Bang A, Kelly O, Eliazer S . Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008; 26(4):443-52. DOI: 10.1038/nbt1393. View

5.
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K . The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003; 113(5):631-42. DOI: 10.1016/s0092-8674(03)00393-3. View