scholarly journals A reduced oxygen tension (5%) is not beneficial for maintaining human embryonic stem cells in the undifferentiated state with short splitting intervals

2008 ◽  
Vol 24 (1) ◽  
pp. 71-80 ◽  
Author(s):  
H.-F. Chen ◽  
H.-C. Kuo ◽  
W. Chen ◽  
F.-C. Wu ◽  
Y.-S. Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Oxygen Tension ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Undifferentiated State

scholarly journals Environmental Oxygen Tension Regulates the Energy Metabolism and Self-Renewal of Human Embryonic Stem Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e62507 ◽  
Author(s):  
Catherine E. Forristal ◽  
David R. Christensen ◽  
Fay E. Chinnery ◽  
Raffaella Petruzzelli ◽  
Kate L. Parry ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Energy Metabolism ◽  
Oxygen Tension ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Self Renewal

scholarly journals Spatio-temporal analyses of OCT4 expression and fate transitions in human embryonic stem cells

2020 ◽  
Author(s):  
Sirio Orozco-Fuentes ◽  
Laura E. Wadkin ◽  
Irina Neganova ◽  
Majlinda Lako ◽  
Rafael A. Barrio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Computational Models ◽  
Probability Distributions ◽  
Embryonic Stem ◽  
Oct4 Expression ◽  
Undifferentiated State ◽  
Spatio Temporal ◽  
The Times

AbstractOCT4 is one of the transcription factors required to maintain an undifferentiated state in human embryonic stem cells (hESCs). Thus, it is crucial to understand how OCT4 transcription is regulated both at the single-cell and colony level. Here we analyse the changes of OCT4-mCherry intensity expression in hESCs in the presence and absence of the BMP4 morphogenetic protein.We show that OCT4 expression is dynamic, reaching a maximum response 10 h after BMP4 treatment. We obtain the stationary probability distributions that govern the hESCs transitions amongst the different cell states in the presence/absence of BMP4 and establish the times at which the hESCs, that lead to differentiated and pluripotent cells, cluster in the colony. Furthermore, by quantifying the similarities between the OCT4 expression amongst neighbouring hESCs, we show that hESCs express, on average, similar values in their local neighbourhood within the first two days of the experiment and before BMP4 treatment. These results are relevant for the development of mathematical and computational models of adherent hESC colonies.

Kynurenine signaling through the aryl hydrocarbon receptor maintains the undifferentiated state of human embryonic stem cells

2019 ◽  
Vol 12 (587) ◽  
pp. eaaw3306 ◽  
Author(s):  
Takako Yamamoto ◽  
Kunitada Hatabayashi ◽  
Mao Arita ◽  
Nobuyuki Yajima ◽  
Chiemi Takenaka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Human Embryonic Stem Cells ◽  
Culture Medium ◽  
Embryonic Stem ◽  
Aryl Hydrocarbon ◽  
Undifferentiated State ◽  
Undifferentiated Escs ◽  
Induced Pluripotent

Kynurenine, which is generated from tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1), binds to the aryl hydrocarbon receptor (AhR). Here, we report that kynurenine was produced by undifferentiated human embryonic stem cells (hESCs) and by induced pluripotent stem cells (iPSCs). In undifferentiated hESCs, kynurenine stimulated the AhR to promote the expression of self-renewal genes. The kynurenine-AhR complex also stimulated the expression of IDO1 and AHR, activating a positive feedback loop. Inhibition of IDO1 activity reduced the proliferation of undifferentiated ESCs but did not stimulate their differentiation. Substantial amounts of free kynurenine were present in the culture medium, providing a paracrine signal for maintenance of the undifferentiated state. Kynurenine was not present in the medium of differentiated ESCs or iPSCs. When ESCs were induced to undergo ectodermal differentiation, the abundance of kynurenine in the medium was reduced through activation of the main kynurenine catabolic pathway mediated by kynurenine aminotransferase 2 (KAT2, also known as AADAT), resulting in the secretion of 2-aminoadipic acid (2-AAA) into the culture medium. Inhibition of KAT2 activity blocked ectodermal differentiation. Thus, kynurenine metabolism plays an important role in the maintenance of the undifferentiated state and in ectodermal differentiation. Furthermore, kynurenine in the culture medium is a biomarker for the undifferentiated state, whereas the presence of 2-AAA in the culture medium is a biomarker of ESCs and iPSCs that have committed to differentiate along the ectoderm lineage.

scholarly journals Analysis of the Factors that Limit the Ability of Feeder Cells to Maintain the Undifferentiated State of Human Embryonic Stem Cells

2009 ◽  
Vol 18 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Luis G. Villa-Diaz ◽  
Crystal Pacut ◽  
Nicole A. Slawny ◽  
Jun Ding ◽  
K. Sue O'Shea ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Feeder Cells ◽  
Undifferentiated State
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