scholarly journals Defining the Role of Wnt/β-Catenin Signaling in the Survival, Proliferation, and Self-Renewal of Human Embryonic Stem Cells

Stem Cells ◽  
2005 ◽  
Vol 23 (10) ◽  
pp. 1489-1501 ◽  
Author(s):  
Gautam Dravid ◽  
Zhaohui Ye ◽  
Holly Hammond ◽  
Guibin Chen ◽  
April Pyle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Self Renewal

scholarly journals Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

2016 ◽  
Vol 113 (42) ◽  
pp. E6382-E6390 ◽  
Author(s):  
Zhuojin Xu ◽  
Aaron M. Robitaille ◽  
Jason D. Berndt ◽  
Kathryn C. Davidson ◽  
Karin A. Fischer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Wnt Proteins ◽  
Primed State

In both mice and humans, pluripotent stem cells (PSCs) exist in at least two distinct states of pluripotency, known as the naïve and primed states. Our understanding of the intrinsic and extrinsic factors that enable PSCs to self-renew and to transition between different pluripotent states is important for understanding early development. In mouse embryonic stem cells (mESCs), Wnt proteins stimulate mESC self-renewal and support the naïve state. In human embryonic stem cells (hESCs), Wnt/β-catenin signaling is active in naïve-state hESCs and is reduced or absent in primed-state hESCs. However, the role of Wnt/β-catenin signaling in naïve hESCs remains largely unknown. Here, we demonstrate that inhibition of the secretion of Wnts or inhibition of the stabilization of β-catenin in naïve hESCs reduces cell proliferation and colony formation. Moreover, we show that addition of recombinant Wnt3a partially rescues cell proliferation in naïve hESCs caused by inhibition of Wnt secretion. Notably, inhibition of Wnt/β-catenin signaling in naïve hESCs did not cause differentiation. Instead, it induced primed hESC-like proteomic and metabolic profiles. Thus, our results suggest that naïve hESCs secrete Wnts that activate autocrine or paracrine Wnt/β-catenin signaling to promote efficient self-renewal and inhibit the transition to the primed state.

scholarly journals PS1 - 158 The Role of LIN28A in Neoplastic Transformation of Human Embryonic Stem Cells (hESCs)

2016 ◽  
Vol 43 (S4) ◽  
pp. S10-S10
Author(s):  
R. Kaur ◽  
L. Liang ◽  
T. Werbowetski-Ogilvie
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Embryonic Stem ◽  
Neoplastic Transformation ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Human Cancers

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

scholarly journals Effects of Ionizing Radiation on Self-Renewal and Pluripotency of Human Embryonic Stem Cells

2010 ◽  
Vol 70 (13) ◽  
pp. 5539-5548 ◽  
Author(s):  
Kitchener D. Wilson ◽  
Ning Sun ◽  
Mei Huang ◽  
Wendy Y. Zhang ◽  
Andrew S. Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ionizing Radiation ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Self Renewal

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 236. Role of P53 on T Lymphopoiesis from Human Embryonic Stem Cells

2016 ◽  
Vol 24 ◽  
pp. S92-S93
Author(s):  
Hiroshi Kohara ◽  
Jiyuan Liao ◽  
Shohei Miyamoto ◽  
Yoko Nagai ◽  
Tomotoshi Marumoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
T Lymphopoiesis
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