scholarly journals Neuroinflammation and EIF2 signaling persist in an HiPSC tri-culture model of HIV infection despite antiretroviral treatment

2019 ◽  
Author(s):  
Sean K. Ryan ◽  
Michael V. Gonzalez ◽  
James P. Garifallou ◽  
Frederick C. Bennett ◽  
Kimberly S. Williams ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Pluripotent Stem Cell ◽  
Antiretroviral Treatment ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Similar Response ◽  
Infection Treatment ◽  
Culture Model ◽  
Key Features ◽  
Induced Pluripotent

AbstractHIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals worldwide, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive. We developed a human-induced pluripotent stem cell (HiPSC) based model; whereby, we independently differentiate HiPSCs into neurons, astrocytes, and microglia and systematically combine to generate a tri-culture with or without HIV-infection and ART. scRNAseq analysis on tri-cultures including HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Remarkably, EFZ alone induced a similar response to infection. Treatment with the antiretroviral compound Efavirenz (EFZ) mostly resolved these signatures; However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa expression. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of HIV infection and its treatment with antiretrovirals.

scholarly journals Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control

2020 ◽  
Author(s):  
Elliot W. Swartz ◽  
Greg Shintani ◽  
Jijun Wan ◽  
Joseph S. Maffei ◽  
Sarah H. Wang ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Calcium Flux ◽  
Electrode Arrays ◽  
Spinal Motor Neurons ◽  
Culture Model ◽  
Skeletal Myotubes ◽  
Induced Pluripotent

SummaryThe failure of the neuromuscular junction (NMJ) is a key component of degenerative neuromuscular disease, yet how NMJs degenerate in disease is unclear. Human induced pluripotent stem cells (hiPSCs) offer the ability to model disease via differentiation toward affected cell types, however, the re-creation of an in vitro neuromuscular system has proven challenging. Here we present a scalable, all-hiPSC-derived co-culture system composed of independently derived spinal motor neurons (MNs) and skeletal myotubes (sKM). In a model of C9orf72-associated disease, co-cultures form functional NMJs that can be manipulated through optical stimulation, eliciting muscle contraction and measurable calcium flux in innervated sKM. Furthermore, co-cultures grown on multi-electrode arrays (MEAs) permit the pharmacological interrogation of neuromuscular physiology. Utilization of this co-culture model as a tunable, patient-derived system may offer significant insights into NMJ formation, maturation, repair, or pathogenic mechanisms that underlie NMJ dysfunction in disease.

scholarly journals Present and future challenges of induced pluripotent stem cells

2015 ◽  
Vol 370 (1680) ◽  
pp. 20140367 ◽  
Author(s):  
Mari Ohnuki ◽  
Kazutoshi Takahashi
Keyword(s):  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Disease Modelling ◽  
Future Perspectives ◽  
Differentiated Cells ◽  
Human Ipscs ◽  
Future Challenges ◽  
Induced Pluripotent

Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability to differentiate into all cell types by enforced expression of defined transcription factors. The discovery of this induced pluripotent stem cell (iPSC) technology has opened up unprecedented opportunities in regenerative medicine, disease modelling and drug discovery. In this review, we introduce the applications and future perspectives of human iPSCs and we also show how iPSC technology has evolved along the way.

scholarly journals Generation of inner ear sensory neurons using blastocyst complementation in a Neurog1+/−−deficient mouse

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aleta R. Steevens ◽  
Matthew W. Griesbach ◽  
Yun You ◽  
James R. Dutton ◽  
Walter C. Low ◽  
...  
Keyword(s):  
Inner Ear ◽  
Sensory Neurons ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Deficient Mouse ◽  
Sensory Deficits ◽  
Blastocyst Complementation ◽  
Induced Pluripotent ◽  
Insight Into

AbstractThis research is the first to produce induced pluripotent stem cell-derived inner ear sensory neurons in the Neurog1+/− heterozygote mouse using blastocyst complementation. Additionally, this approach corrected non-sensory deficits associated with Neurog1 heterozygosity, indicating that complementation is specific to endogenous Neurog1 function. This work validates the use of blastocyst complementation as a tool to create novel insight into the function of developmental genes and highlights blastocyst complementation as a potential platform for generating chimeric inner ear cell types that can be transplanted into damaged inner ears to improve hearing.

scholarly journals Induced pluripotent stem cell technology for modelling and therapy of cerebellar ataxia

Open Biology ◽  
2015 ◽  
Vol 5 (7) ◽  
pp. 150056 ◽  
Author(s):  
Lauren M. Watson ◽  
Maggie M. K. Wong ◽  
Esther B. E. Becker
Keyword(s):  
Stem Cell ◽  
Cerebellar Ataxia ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Disease Modelling ◽  
Stem Cell Technology ◽  
Induced Pluripotent ◽  
First Descriptions ◽  
Made In

Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinson's disease and Alzheimer's disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous group of conditions and explore the challenges associated with generating cerebellar neurons from iPSCs, which have thus far hindered the expansion of this research.

scholarly journals The iPSC proteomic compendium

2018 ◽  
Author(s):  
Alejandro Brenes ◽  
Dalila Bensaddek ◽  
Jens Hukelmann ◽  
Vackar Afzal ◽  
Angus I. Lamond
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Expression Profiles ◽  
Induced Pluripotent Stem Cell ◽  
Mass Spectrometry Data ◽  
Spectral Library ◽  
Phenotypic Data ◽  
Key Features ◽  
Induced Pluripotent ◽  
Proteomic Map

AbstractInduced pluripotent stem cell (iPSC) technology holds great potential for therapeutic and research purposes. The Human Induced Pluripotent Stem Cell Initiative (HipSci) was established to generate a panel of high-quality iPSCs, from healthy and disease cohorts, with accompanying multi-omics and phenotypic data. Here, we present a proteomic analysis of 217 HipSci iPSC lines obtained from 163 donors.This dataset provides a comprehensive proteomic map of iPSCs, identifying >16,000 protein groups. We analyse how the expression profiles of proteins involved in cell cycle, metabolism and DNA repair contribute to key features of iPSC biology and we identify potential new regulators of the primed pluripotent state. To facilitate access, all these data have been integrated into the Encyclopedia of Proteome Dynamics (www.peptracker.com/epd), where it can be browsed interactively. Additionally, we generated an iPSC specific spectral library for DIA which we deposited in PRIDE along with the raw and processed mass-spectrometry data.

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