scholarly journals A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation

2005 ◽  
Vol 170 (2) ◽  
pp. 305-316 ◽  
Author(s):  
Yingwei Mao ◽  
Angel W.-M. Lee
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Akt Activation ◽  
Important Player ◽  
Ec Cells ◽  
Phosphoinositide 3 Kinase ◽  
Induced Apoptosis ◽  
Constitutively Active

Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by basic FGF (bFGF). In EC cells, Gab2 silencing results in hypersensitivity to RA-induced apoptosis and abrogates the protection by bFGF. Gab2 suppression reduces bFGF-dependent activation of AKT but not ERK, and constitutively active AKT, but not constitutively active MEK1, reverses the hypersensitization. Thus, Gab2-mediated AKT activation is required for bFGF's protection. Moreover, Gab2 silencing impairs the differentiation of EC cells to neurons. Similarly, in NSCs, Gab2 suppression reduces bFGF-dependent proliferation as well as neuronal survival and production upon differentiation. Our findings provide the first evidence that Gab2 is an important player in neural differentiation, partly by acting downstream of bFGF to mediate survival through phosphoinositide 3 kinase–AKT.

scholarly journals Tumorigenic and Differentiation Potentials of Embryonic Stem Cells Depend on TGFβFamily Signaling: Lessons from Teratocarcinoma Cells Stimulated to Differentiate with Retinoic Acid

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Olga Gordeeva ◽  
Sergey Khaydukov
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Es Cells ◽  
Embryonic Stem ◽  
Activin A ◽  
Bmp Signaling ◽  
Induced Differentiation ◽  
Ec Cells

A significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand the mechanisms of incomplete differentiation, a comparative study of retinoic acid-induced differentiation of mouse embryonic stem (ES) and teratocarcinoma (EC) cells was conducted. The present study identified differences in proliferative activity, differentiation, and tumorigenic potentials between ES and EC cells. Higher expression of Nanog and Mvh, as well as Activin A and BMP4, was found in undifferentiated ES cells than in EC cells. However, the expression levels of Activin A and BMP4 increased more sharply in the EC cells during retinoic acid-induced differentiation. Stimulation of the Activin/Nodal and BMP signaling cascades and inhibition of the MEK/ERK and PI3K/Act signaling pathways resulted in a significant decrease in the number of Oct4-expressing ES cells and a loss of tumorigenicity, similar to retinoic acid-stimulated EC cells. Thus, this study demonstrates that a differentiation strategy that modulates prodifferentiation and antiproliferative signaling in ES cells may be effective for eliminating tumorigenic cells and may represent a valuable tool for the development of safe stem cell therapeutics.

scholarly journals Leucine-Rich Repeat Kinase 2 Modulates Retinoic Acid-Induced Neuronal Differentiation of Murine Embryonic Stem Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20820 ◽  
Author(s):  
Cathrin Schulz ◽  
Marie Paus ◽  
Katharina Frey ◽  
Ramona Schmid ◽  
Zacharias Kohl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Leucine Rich Repeat ◽  
Murine Embryonic Stem Cells

Phosphoinositide 3-kinase inhibition enables retinoic acid-induced neurogenesis in monolayer culture of embryonic stem cells

2012 ◽  
Vol 113 (2) ◽  
pp. 563-570 ◽  
Author(s):  
Hana Kotasová ◽  
Iva Veselá ◽  
Jan Kučera ◽  
Zbyněk Houdek ◽  
Jiřina Procházková ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Embryonic Stem Cells ◽  
Monolayer Culture ◽  
Embryonic Stem ◽  
Kinase Inhibition ◽  
Phosphoinositide 3 Kinase

scholarly journals Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1078
Author(s):  
Tae Won Ha ◽  
Ji Hun Jeong ◽  
HyeonSeok Shin ◽  
Hyun Kyu Kim ◽  
Jeong Suk Im ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Pluripotent Stem Cells ◽  
Meta Analysis ◽  
Embryonic Stem ◽  
Structural Features ◽  
Human Pluripotent Stem Cells ◽  
Differentiated Cells ◽  
Induced Apoptosis

Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress.

scholarly journals Human Embryonic Stem Cells Have Constitutively Active Bax at the Golgi and Are Primed to Undergo Rapid Apoptosis

2012 ◽  
Vol 46 (5) ◽  
pp. 573-583 ◽  
Author(s):  
Raluca Dumitru ◽  
Vivian Gama ◽  
B. Matthew Fagan ◽  
Jacquelyn J. Bower ◽  
Vijay Swahari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Constitutively Active

Retinoic Acid-Polyethyleneimine Complex Nanoparticles for Embryonic Stem Cell-Derived Neuronal Differentiation

Langmuir ◽  
2013 ◽  
Vol 29 (31) ◽  
pp. 9857-9862 ◽  
Author(s):  
Boram Ku ◽  
Ji-eun Kim ◽  
Bong Hyun Chung ◽  
Bong Geun Chung
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Embryonic Stem Cell ◽  
Neuronal Differentiation ◽  
Embryonic Stem

scholarly journals Dual Inhibition of Activin/Nodal/TGF-βand BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Vedavathi Madhu ◽  
Abhijit S. Dighe ◽  
Quanjun Cui ◽  
D. Nicole Deal
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neuronal Differentiation ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Bmp Signaling ◽  
Specific Marker ◽  
Adipose Derived Stem Cells ◽  
Neuronal Marker ◽  
Dual Inhibition

Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-βand BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally,in vitrosubcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

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