scholarly journals A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm

2019 ◽  
Author(s):  
George Britton ◽  
Idse Heemskerk ◽  
Rachel Hodge ◽  
Amina A Qutub ◽  
Aryeh Warmflash
Keyword(s):  
Wnt Signaling ◽  
Control Parameter ◽  
Embryonic Stem ◽  
Cell System ◽  
Neural Plate ◽  
Model Organisms ◽  
Directed Differentiation ◽  
Neural Plate Border ◽  
Stem Cell System

SummaryDuring development, the ectoderm is patterned by a combination of BMP and WNT signaling. Research in model organisms has provided substantial insight, however, there are currently no systems to study this patterning in humans. Further, the complexity of neural plate border specification has made it difficult to transition from discovering the genes involved to deeper mechanistic understanding. Here, we develop an in vitro model of human ectodermal patterning, in which hESCs self-organize to form robust and quantitatively reproducible patterns corresponding to the dorsal-ventral axis of the embryo. Using this platform, we show that the duration of endogenous WNT signaling is a crucial control parameter, and that cells sense relative levels of BMP and WNT signaling in making fate decisions. These insights allowed us to develop an improved protocol for placodal differentiation. Thus, our platform is a powerful tool for studying human ectoderm patterning and for improving directed differentiation protocols.

scholarly journals Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo

2015 ◽  
Vol 13 (1) ◽  
pp. 720-730 ◽  
Author(s):  
LIPING OU ◽  
LIAOQIONG FANG ◽  
HEJING TANG ◽  
HAI QIAO ◽  
XIAOMEI ZHANG ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

Abstract 1457: IGFBP-4-Mediated Wnt Inhibition is Required for Cardiac Myogenesis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Weidong Zhu ◽  
Ichiro Shiojima ◽  
Li Zhi ◽  
Hiroyuki Ikeda ◽  
Masashi Yoshida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Wnt Signaling ◽  
Heart Diseases ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cardiomyocyte Differentiation ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Insulin-like growth factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the effects of IGFBPs appear to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. In this study we demonstrate that IGFBP-4 is a novel cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells and embryonic stem (ES) cells in vitro. Conversely, siRNA-mediated knockdown of IGFBP-4 in P19CL6 cells or ES cells attenuated cardiomyocyte differentiation, and morpholino-mediated knockdown of IGFBP-4 in Xenopus embryos resulted in severe cardiac defects and complete absence of the heart in extreme cases. We also demonstrate that the cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signaling. IGFBP-4 physically interacted with a Wnt receptor Frizzled 8 (Frz8) and a Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Moreover, the cardiogenic defects induced by IGFBP-4 knockdown both in vitro and in vivo was rescued by simultaneous inhibition of canonical Wnt signaling. Thus, IGFBP-4 is an inhibitor of the canonical Wnt signaling, and Wnt inhibition by IGFBP-4 is required for cardiogenesis. The present study provides a molecular link between IGF signaling and Wnt signaling, and suggests that IGFBP-4 may be a novel therapeutic target for heart diseases.

scholarly journals A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm

Development ◽  
2019 ◽  
Vol 146 (20) ◽  
pp. dev179093 ◽  
Author(s):  
George Britton ◽  
Idse Heemskerk ◽  
Rachel Hodge ◽  
Amina A. Qutub ◽  
Aryeh Warmflash
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell System ◽  
Stem Cell System ◽  
Self Organizing

scholarly journals Transcription factor directed differentiation of embryonic stem cells in vitro

2009 ◽  
Vol 92 (3) ◽  
pp. S172
Author(s):  
R.M. Anchan ◽  
S.A. Lachke ◽  
B. Gerami-Naini ◽  
K.E. Naber ◽  
J. Eaton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Directed Differentiation

scholarly journals Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Divya S. Varghese ◽  
Shama Parween ◽  
Mustafa T. Ardah ◽  
Bright Starling Emerald ◽  
Suraiya A. Ansari
Keyword(s):  
Cell Viability ◽  
Disease Modeling ◽  
Culture Media ◽  
Embryonic Stem ◽  
Toxicity Testing ◽  
Cell Types ◽  
Specific Cell ◽  
Directed Differentiation ◽  
Embryonic Neurogenesis

Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear. In this study, we found that antibiotics, pen-strep, and gentamicin did not affect hESC cell viability or expression of pluripotency markers. However, during directed differentiation towards neural and hepatic fate, significant cell death was noted through the activation of caspase cascade. Also, the expression of neural progenitor markers Pax6, Emx2, Otx2, and Pou3f2 was significantly reduced suggesting that gentamicin may adversely affect early embryonic neurogenesis whereas no effect was seen on the expression of endoderm or hepatic markers during differentiation. Our results suggest that the use of antibiotics in cell culture media for the maintenance and differentiation of hESCs needs thorough investigation before use to avoid erroneous results.

Live Monitoring of the Endoderm�like Cell Differentiation in the Murine Embryonic Stem Cell System

2004 ◽  
Vol 2004 (Fall) ◽  
Author(s):  
Irina Drobinskaya ◽  
Lubov Rochlina ◽  
Thomas Linn ◽  
Reinhard Bretzel ◽  
Eugen Kolossov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell System ◽  
Murine Embryonic Stem Cell ◽  
Stem Cell System
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