scholarly journals Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 987 ◽  
Author(s):  
Peter M.J. Quinn ◽  
Jan Wijnholds
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Cell Polarity ◽  
Apical Cell ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Downstream Signaling ◽  
Fetal Retina ◽  
Crumbs Complex

The Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regulating junctional structures and cell adhesion. The Crumbs complex acts as a conductor orchestrating multiple downstream signaling pathways in epithelial and neuronal tissue development. These pathways lead to the regulation of cell size, cell fate, cell self-renewal, proliferation, differentiation, migration, mitosis, and apoptosis. In retinogenesis, these are all pivotal processes with important roles for the Crumbs complex to maintain proper spatiotemporal cell processes. Loss of Crumbs function in the retina results in loss of the stratified appearance resulting in retinal degeneration and loss of visual function. In this review, we begin by discussing the physiology of vision. We continue by outlining the processes of retinogenesis and how well this is recapitulated between the human fetal retina and human embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal organoids. Additionally, we discuss the functionality of in utero and preterm human fetal retina and the current level of functionality as detected in human stem cell-derived organoids. We discuss the roles of apical-basal cell polarity in retinogenesis with a focus on Leber congenital amaurosis which leads to blindness shortly after birth. Finally, we discuss Crumbs homolog (CRB)-based gene augmentation.

scholarly journals Interaction of retinoic acid and scl controls primitive blood development

Blood ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Jill L. O. de Jong ◽  
Alan J. Davidson ◽  
Yuan Wang ◽  
James Palis ◽  
Praise Opara ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Erythroid Progenitors ◽  
Self Renewal ◽  
Hematopoietic Development ◽  
Blood Island ◽  
Primitive Hematopoiesis

Abstract Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation. Here, we demonstrate that RA decreases gata1 expression and blocks primitive hematopoiesis in zebrafish (Danio rerio) embryos, while increasing expression of the vascular marker, fli1. Treatment with an inhibitor of RA biosynthesis or a retinoic acid receptor antagonist increases gata1+ erythroid progenitors in the posterior mesoderm of wild-type embryos and anemic cdx4−/− mutants, indicating a link between the cdx-hox signaling pathway and RA. Overexpression of scl, a DNA binding protein necessary for hematopoietic development, rescues the block of hematopoiesis induced by RA. We show that these effects of RA and RA pathway inhibitors are conserved during primitive hematopoiesis in murine yolk sac explant cultures and embryonic stem cell assays. Taken together, these data indicate that RA inhibits the commitment of mesodermal cells to hematopoietic fates, functioning downstream of cdx4 and upstream of scl. Our studies establish a new connection between RA and scl during development that may participate in stem cell self-renewal and hematopoietic differentiation.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Microvesicles Transmit RNAs and Proteins to Recipient Mature Heart Cells Modulating Cell Fate and Behavior

Stem Cells ◽  
2015 ◽  
Vol 33 (9) ◽  
pp. 2748-2761 ◽  
Author(s):  
Sylwia Bobis-Wozowicz ◽  
Katarzyna Kmiotek ◽  
Malgorzata Sekula ◽  
Sylwia Kedracka-Krok ◽  
Elzbieta Kamycka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Heart Cells ◽  
Induced Pluripotent ◽  
And Behavior ◽  
Fate And Behavior

Abstract 16007: Functional Comparison of Human Embryonic Stem Cell- versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Rat Ischemic Myocardial Infarction Model

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Wenyi Chen ◽  
Johannes Riegler ◽  
Elena Matsa ◽  
Qi Shen ◽  
Haodi Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Cardiac Function ◽  
Embryonic Stem Cell ◽  
Pluripotent Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Induced Pluripotent

Introduction: Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as an unlimited cell source for cardiac regenerative therapy. However, the functional equivalency of both approaches has not been previously reported. Here we performed head-to-head comparison on the beneficial effects of ESC-CM and iPSC-CMs in restoring cardiac function in a rat myocardial infarction (MI) model. Methods & Results: Human ESCs and iPSCs were differentiated into cardiomyocytes using small molecules. FACS analysis confirmed ~85% and ~83% of cells differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T, and immunofluorescence staining demonstrated that ESC-CMs and iPSC-CMs have striated sarcomeric structure (Figure A-B). Both ESC-CMs and iPSC-CMs displayed similar maturity for calcium handling (transient amplitude: ΔF/F 0 = 3.8±0.3; time to peak: ~200 ms; 50% transient duration: ~400 ms). qRT-PCR showed that ESC-CMs and iPSC-CMs expressed CASQ2, GJA5, KCNJ2, KCNJ5, MYH6, MYH7, and SCN5A at comparable levels to human fetal heart tissue. Next, ESC-CMs and iPSC-CMs were injected into the left ventricular free wall of infarcted hearts (adult nude rats; n=14, 10, respectively). Cardiac function was assessed by MRI one month post cell injection and the hearts were harvested and stained for human cardiac markers. Both ESC-CMs and iPSC-CMs could engraft in ischemic rat hearts (Figure C). Comprehensive functional analysis with small animal magnetic resonance imaging (MRI), echocardiography, and pressure-volume loop analysis are underway. Conclusion: We set out to perform head to head comparison for the first time that iPSC-CMs may facilitate cardiac repair at comparable levels to ESC-CMs. Unlike allogeneic ESC-CM therapy, autologous iPSC-CMs could be used to overcome immune rejection for cardiac cell transplantation in the future.

scholarly journals Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions

PLoS Genetics ◽  
2011 ◽  
Vol 7 (6) ◽  
pp. e1002130 ◽  
Author(s):  
Kian Leong Lee ◽  
Sandy Keat Lim ◽  
Yuriy Lvovich Orlov ◽  
Le Yau Yit ◽  
Henry Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Activin Signaling

scholarly journals Induced Pluripotent Stem Cell as a New Source for Cancer Immunotherapy

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Farzaneh Rami ◽  
Halimeh Mollainezhad ◽  
Mansoor Salehi
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Pluripotent Stem Cell ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Protective Function ◽  
Induced Pluripotent

The immune system consists of cells, proteins, and other molecules that beside each other have a protective function for the host against foreign pathogens. One of the most essential features of the immune system is distinguishability between self- and non-self-cells. This function has an important role in limiting development and progression of cancer cells. In this case, the immune system can detect tumor cell as a foreign pathogen; so, it can be effective in elimination of tumors in their early phases of development. This ability of the immune system resulted in the development of a novel therapeutic field for cancer treatment using host immune components which is called cancer immunotherapy. The main purpose of cancer immunotherapy is stimulation of a strong immune response against the tumor cells that can result from expressing either the immune activator cytokines in the tumor area or gene-modified immune cells. Because of the problems of culturing and manipulating immune cells ex vivo, in recent years, embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) have been used as new sources for generation of modified immune stimulatory cells. In this paper, we reviewed some of the progressions in iPSC technology for cancer immunotherapy.

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