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OCT4 and PAX6 determine the dual function of SOX2 in human ESCs as a key pluripotent or neural factor

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Title: OCT4 and PAX6 determine the dual function of SOX2 in human ESCs as a key pluripotent or neural factor
Authors: Cui, W
Zhang, S
Bell, E
Zhi, H
Brown, S
Muhammad Imran, SA
Azuara, V
Item Type: Journal Article
Abstract: Background Sox2 is a well-established pluripotent transcription factor that plays an essential role in establishing and maintaining pluripotent stem cells (PSCs). It is also thought to be a linage specifier that governs PSC neural lineage specification upon their exiting the pluripotent state. However, the exact role of SOX2 in human PSCs was still not fully understood. In this study, we studied the role of SOX2 in human embryonic stem cells (hESCs) by gain- and loss-of-function approaches and explored the possible underlying mechanisms. Results We demonstrate that knockdown of SOX2 induced hESC differentiation to endoderm-like cells, whereas overexpression of SOX2 in hESCs enhanced their pluripotency under self-renewing culture conditions but promoted their neural differentiation upon replacing the culture to non-self-renewal conditions. We show that this culture-dependent dual function of SOX2 was probably attributed to its interaction with different transcription factors predisposed by the culture environments. Whilst SOX2 interacts with OCT4 under self-renewal conditions, we found that, upon neural differentiation, PAX6, a key neural transcription factor, is upregulated and shows interaction with SOX2. The SOX2-PAX6 complex has different gene regulation pattern from that of SOX2-OCT4 complex. Conclusions Our work provides direct evidence that SOX2 is necessarily required for hESC pluripotency; however, it can also function as a neural factor, depending on the environmental input. OCT4 and PAX6 might function as key SOX2-interacting partners that determine the function of SOX2 in hESCs.
Issue Date: 18-Apr-2019
Date of Acceptance: 29-Mar-2019
URI: http://hdl.handle.net/10044/1/69874
DOI: https://dx.doi.org/10.1186/s13287-019-1228-7
ISSN: 1757-6512
Publisher: BMC
Journal / Book Title: Stem Cell Research and Therapy
Volume: 10
Copyright Statement: © The Author(s). 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
SOX2
OCT4
PAX6
Neural differentiation
Human embryonic stem cells
EMBRYONIC STEM-CELLS
SELF-RENEWAL
DIFFERENTIATION
MOUSE
SPECIFICATION
FIBROBLASTS
MAINTENANCE
LINEAGES
COMPLEX
CULTURE
10 Technology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Article Number: ARTN 122
Appears in Collections:Department of Surgery and Cancer