scholarly journals Mapping Gene Circuits Essential for Germ Layer Differentiation via Loss-of-Function Screens in Haploid Human Embryonic Stem Cells

2020 ◽  
Vol 27 (4) ◽  
pp. 679-691.e6
Author(s):  
Atilgan Yilmaz ◽  
Carmel Braverman-Gross ◽  
Anna Bialer-Tsypin ◽  
Mordecai Peretz ◽  
Nissim Benvenisty
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Germ Layer ◽  
Loss Of Function ◽  
Gene Circuits ◽  
Mapping Gene ◽  
Germ Layer Differentiation

scholarly journals The influence of scaffold elasticity on germ layer specification of human embryonic stem cells

Biomaterials ◽  
2011 ◽  
Vol 32 (36) ◽  
pp. 9612-9621 ◽  
Author(s):  
Janet Zoldan ◽  
Emmanouil D. Karagiannis ◽  
Christopher Y. Lee ◽  
Daniel G. Anderson ◽  
Robert Langer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Germ Layer

scholarly journals Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Bret Sanders ◽  
Daniel D’Andrea ◽  
Mark O. Collins ◽  
Elliott Rees ◽  
Tom G. J. Steward ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Human Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Neuropsychiatric Disorders ◽  
Loss Of Function ◽  
Excitatory Neurons

AbstractCoordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. We identify transcriptional programs expressed during early neurogenesis in vitro and in human foetal cortex that are down-regulated in DLG2−/− lines. Down-regulation impacted neuronal differentiation and maturation, impairing migration, morphology and action potential generation. Genetic variation in these programs is associated with neuropsychiatric disorders and cognitive function, with associated variants predominantly concentrated in loss-of-function intolerant genes. Neurogenic programs also overlap schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways active during prenatal cortical development may also be associated with mature neuronal dysfunction. Our data from human embryonic stem cells, when combined with analysis of available foetal cortical gene expression data, de novo rare variants and GWAS statistics for neuropsychiatric disorders and cognition, reveal a convergence on transcriptional programs regulating excitatory cortical neurogenesis.

scholarly journals miR-125b Promotes Early Germ Layer Specification through Lin28/let-7d and Preferential Differentiation of Mesoderm in Human Embryonic Stem Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e36121 ◽  
Author(s):  
Sharon S. Y. Wong ◽  
Carissa Ritner ◽  
Sweta Ramachandran ◽  
Julian Aurigui ◽  
Cameron Pitt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Germ Layer

scholarly journals Soluble Amyloid Precursor Protein Induces Rapid Neural Differentiation of Human Embryonic Stem Cells

2011 ◽  
Vol 286 (27) ◽  
pp. 24264-24274 ◽  
Author(s):  
Kristine K. Freude ◽  
Mahmud Penjwini ◽  
Joy L. Davis ◽  
Frank M. LaFerla ◽  
Mathew Blurton-Jones
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Amyloid Precursor Protein ◽  
Human Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
Precursor Protein ◽  
Stem Cell Marker ◽  
Loss Of Function ◽  
Neural Lineage

Human embryonic stem cells (hESCs) offer tremendous potential for not only treating neurological disorders but also for their ability to serve as vital reagents to model and investigate human disease. To further our understanding of a key protein involved in Alzheimer disease pathogenesis, we stably overexpressed amyloid precursor protein (APP) in hESCs. Remarkably, we found that APP overexpression in hESCs caused a rapid and robust differentiation of pluripotent stem cells toward a neural fate. Despite maintenance in standard hESC media, up to 80% of cells expressed the neural stem cell marker nestin, and 65% exhibited the more mature neural marker β-3 tubulin within just 5 days of passaging. To elucidate the mechanism underlying the effects of APP on neural differentiation, we examined the proteolysis of APP and performed both gain of function and loss of function experiments. Taken together, our results demonstrate that the N-terminal secreted soluble forms of APP (in particular sAPPβ) robustly drive neural differentiation of hESCs. Our findings not only reveal a novel and intriguing role for APP in neural lineage commitment but also identify a straightforward and rapid approach to generate large numbers of neurons from human embryonic stem cells. These novel APP-hESC lines represent a valuable tool to investigate the potential role of APP in development and neurodegeneration and allow for insights into physiological functions of this protein.

Ethanol alters cell cycle gene expression in human embryonic stem cells

2016 ◽  
Vol 01 (03) ◽  
pp. 201-208 ◽  
Author(s):  
Malini Krishnamoorthy ◽  
Brian Gerwe ◽  
Jamie Heimburg-Molinaro ◽  
Rachel Nash ◽  
Jagan Arumugham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Cycle Gene ◽  
Cell Cycle Gene Expression
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