Evidence map›Paper›PMID 30999923›Full record

ArticleStem cell research & therapy2019

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

Shuchen Zhang, Emma Bell, Huihan Zhi, Sarah Brown, Siti A M Imran, Véronique Azuara, Wei Cui

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Expression status transition ofF1000Research · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Shuchen ZhangInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Emma BellInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Huihan ZhiInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Sarah BrownInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Siti A M ImranInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Véronique AzuaraInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Wei CuiInstitute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK. wei.cui@imperial.ac.uk.ORCID 0000-0003-2019-380X
Imperial College London · GBPrincess Margaret Cancer Centre · CA

Funding

Medical Research Council
6 · The paper itself

Abstract

backgroundSox2 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.

resultsWe 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.

conclusionsOur 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.

Indexed as

Cell DifferentiationCell LineHuman Embryonic Stem CellsHumansNeural Stem CellsOctamer Transcription Factor-3PAX6 Transcription FactorSOXB1 Transcription FactorsOctamer Transcription Factor-3PAX6 protein, humanPAX6 Transcription FactorPOU5F1 protein, humanSOX2 protein, humanSOXB1 Transcription FactorsHuman embryonic stem cellsNeural differentiationOCT4PAX6SOX2

Identifiers

PMID30999923
PMCPMC6471829
OpenAlexW2946240913

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.