Unravelling the pluripotency paradox in fetal and placental mesenchymal stem cells: Oct-4 expression and the case of the emperor's new clothes

Ryan, Jennifer M., Pettit, Allison R, Guillot, Pascale V, Chan, Jerry K. Y. and Fisk, Nicholas M. (2011) Unravelling the pluripotency paradox in fetal and placental mesenchymal stem cells: Oct-4 expression and the case of the emperor's new clothes. Stem Cell Reviews and Reports, 9 4: 408-421. doi:10.1007/s12015-011-9336-5


Author Ryan, Jennifer M.
Pettit, Allison R
Guillot, Pascale V
Chan, Jerry K. Y.
Fisk, Nicholas M.
Title Unravelling the pluripotency paradox in fetal and placental mesenchymal stem cells: Oct-4 expression and the case of the emperor's new clothes
Journal name Stem Cell Reviews and Reports   Check publisher's open access policy
ISSN 1550-8943
1558-6804
Publication date 2011-12-11
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s12015-011-9336-5
Open Access Status Not yet assessed
Volume 9
Issue 4
Start page 408
End page 421
Total pages 14
Place of publication Totowa, NJ, United States
Publisher Humana Press
Language eng
Abstract Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT- 4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT- 4 expression is insufficient to induce true "stemness", but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT- 4 in fetal or adnexal MSC to show that most studies report OCT- 4 message or protein expression, but no study provides definitive evidence of true OCT- 4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT- 4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT- 4 isoform (OCT- 4A) associated with pluripotency. Although specific detection of OCT- 4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT- 4A and the pseudogene OCT- 4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT- 4A (or by default OCT- 4B). Reports suggesting OCT- 4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT- 4 literature leads us to suggest that OCT- 4 expression in fetal MSC may be a case of "The Emperor's New Clothes" with early reports of (false) positive expression amplified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.
Formatted abstract
Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT- 4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT- 4 expression is insufficient to induce true "stemness", but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT- 4 in fetal or adnexal MSC to show that most studies report OCT- 4 message or protein expression, but no study provides definitive evidence of true OCT- 4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT- 4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT- 4 isoform (OCT- 4A) associated with pluripotency. Although specific detection of OCT- 4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT- 4A and the pseudogene OCT- 4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT- 4A (or by default OCT- 4B). Reports suggesting OCT- 4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT- 4 literature leads us to suggest that OCT- 4 expression in fetal MSC may be a case of "The Emperor's New Clothes" with early reports of (false) positive expression amplified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.
Keyword Mesenchymal stem cells
MSC
Fetal-placental tissue
Pluripotency
OCT-4
Stemness
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: December 11, 2011

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2012 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 17 Feb 2012, 01:34:15 EST by Jennifer Ryan on behalf of UQ Centre for Clinical Research