scholarly journals Network Activity Development in Cultured Cortical Neurons: Comparison Between Rat Embryonic and Human Pluripotent Stem Cell -Derived Systems

2018 ◽  
Vol 12 ◽  
Author(s):  
Tanja Hyvärinen ◽  
Anu Hyysalo ◽  
Emre Kapucu ◽  
Susanna Narkilahti
Keyword(s):  
Stem Cell ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Network Activity ◽  
Human Pluripotent Stem Cell ◽  
Cultured Cortical Neurons

scholarly journals Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tanja Hyvärinen ◽  
Anu Hyysalo ◽  
Fikret Emre Kapucu ◽  
Laura Aarnos ◽  
Andrey Vinogradov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Microelectrode Array ◽  
Functional Characterization ◽  
Principal Component ◽  
Network Activity ◽  
Human Pluripotent Stem Cell ◽  
Cortical Networks ◽  
Cortical Cultures

AbstractHuman pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.

scholarly journals Human Pluripotent Stem Cell-derived Cortical Neurons for High Throughput Medication Screening in Autism: A Proof of Concept Study in SHANK3 Haploinsufficiency Syndrome

EBioMedicine ◽  
2016 ◽  
Vol 9 ◽  
pp. 293-305 ◽  
Author(s):  
Hélène Darville ◽  
Aurélie Poulet ◽  
Frédérique Rodet-Amsellem ◽  
Laure Chatrousse ◽  
Julie Pernelle ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Throughput ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Proof Of Concept ◽  
Human Pluripotent Stem Cell ◽  
Concept Study ◽  
Medication Screening

scholarly journals Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way

Cell Reports ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2732-2743 ◽  
Author(s):  
Ira Espuny-Camacho ◽  
Kimmo A. Michelsen ◽  
Daniele Linaro ◽  
Angéline Bilheu ◽  
Sandra Acosta-Verdugo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Visual Cortex ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell

scholarly journals Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry

2020 ◽  
Author(s):  
Marita Grønning Hansen ◽  
Cecilia Laterza ◽  
Sara Palma‐Tortosa ◽  
Giedre Kvist ◽  
Emanuela Monni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Neural Circuitry ◽  
Human Pluripotent Stem Cell ◽  
Adult Human

scholarly journals Gene regulatory network (GRN) embedded agents connect cellular decision making to human pluripotent stem cell derived germ layer-like pattern formation

2020 ◽  
Author(s):  
Himanshu Kaul ◽  
Nicolas Werschler ◽  
Mukul Tewary ◽  
Andrew Hagner ◽  
Joel Ostblom ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Pluripotent Stem Cell ◽  
Network Activity ◽  
Germ Layer ◽  
Human Pluripotent Stem Cell ◽  
Gene Regulatory

ABSTRACTThe emergence of germ layers in embryos during gastrulation is a key developmental milestone. How morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. To understand this, we developed a gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into ‘cellular’ agents that respond to a dynamic signalling microenvironment. We found that cellular pattern order, composition, and dynamics were predictably manipulable based on the GRN wiring. We showed that feedback between OCT4, and BMP and WNT pathways created a dynamic OCT4 front that mediates the spatiotemporal evolution of developmental patterns. Translocation of this radial front can be predictively disrupted in vitro to control germ-layer pattern composition. This work links the emergence of multicellular patterns to regulatory network activity in individual hPSCs. We anticipate our approach will help to understand how GRN structure regulates organogenesis in different contexts.

scholarly journals JIP2 haploinsufficiency contributes to neurodevelopmental abnormalities in human pluripotent stem cell–derived neural progenitors and cortical neurons

2018 ◽  
Vol 1 (4) ◽  
pp. e201800094 ◽  
Author(s):  
Reinhard Roessler ◽  
Johanna Goldmann ◽  
Chikdu Shivalila ◽  
Rudolf Jaenisch
Keyword(s):  
Stem Cell ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Neural Progenitor Cells ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Human Pluripotent Stem Cell ◽  
Cellular Mechanisms ◽  
Mature Neurons ◽  
Neurodevelopmental Abnormalities

Phelan–McDermid syndrome (also known as 22q13.3 deletion syndrome) is a syndromic form of autism spectrum disorder and currently thought to be caused by heterozygous loss of SHANK3. However, patients most frequently present with large chromosomal deletions affecting several additional genes. We used human pluripotent stem cell technology and genome editing to further dissect molecular and cellular mechanisms. We found that loss of JIP2 (MAPK8IP2) may contribute to a distinct neurodevelopmental phenotype in neural progenitor cells (NPCs) affecting neuronal maturation. This is most likely due to a simultaneous down-regulation of c-Jun N-terminal kinase (JNK) proteins, leading to impaired generation of mature neurons. Furthermore, semaphorin signaling appears to be impaired in patient NPCs and neurons. Pharmacological activation of neuropilin receptor 1 (NRP1) rescued impaired semaphorin pathway activity and JNK expression in patient neurons. Our results suggest a novel disease-specific mechanism involving the JIP/JNK complex and identify NRP1 as a potential new therapeutic target.

scholarly journals JIP2 haploinsufficiency contributes to neurodevelopmental abnormalities in human pluripotent stem cell-derived neural progenitors and cortical neurons

2017 ◽  
Author(s):  
Reinhard Roessler ◽  
Johanna Goldmann ◽  
Chikdu Shivalila ◽  
Rudolf Jaenisch
Keyword(s):  
Stem Cell ◽  
Cortical Neurons ◽  
Pluripotent Stem Cell ◽  
Autism Spectrum ◽  
Neural Progenitors ◽  
Deletion Syndrome ◽  
Human Pluripotent Stem Cell ◽  
Cellular Mechanisms ◽  
Mature Neurons ◽  
Neurodevelopmental Abnormalities

AbstractPhelan-McDermid syndrome (also known as 22q13 deletion syndrome) is a syndromic form of autism spectrum disorder and currently thought to be caused by heterozygous loss of SHANK3. However, patients most frequently present with large chromosomal deletions affecting several additional genes. We used human pluripotent stem cell technology and genome editing to further dissect molecular and cellular mechanisms. We found that loss of JIP2 (MAPK8IP2) may contribute to a distinct neurodevelopmental phenotype in neural progenitors (NPCs) affecting neuronal maturation. This is most likely due to simultaneous misregulation of JNK proteins, leading to impaired generation of mature neurons. Furthermore, semaphorin signaling is compromised in patient NPCs and neurons. Pharmacological stimulation of neuropilin receptor 1 (NRP1) rescued impaired semaphorin pathway activity and JNK expression in patient neurons. Our results suggest a novel disease-specific mechanism involving the JIP/JNK complex and identify NRP1 as potential therapeutic target.

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