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 ◽  
...  

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.

2020 ◽  
Author(s):  
Aleta R. Steevens ◽  
Matthew W. Griesbach ◽  
Yun You ◽  
James R. Dutton ◽  
Walter C. Low ◽  
...  

Abstract This 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.


2020 ◽  
Author(s):  
Aleta R. Steevens ◽  
Matthew W. Griesbach ◽  
Yun You ◽  
James R. Dutton ◽  
Walter C. Low ◽  
...  

Abstract This 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 inner ear cell types that can be transplanted into damaged inner ears to improve hearing.


2015 ◽  
Vol 370 (1680) ◽  
pp. 20140367 ◽  
Author(s):  
Mari Ohnuki ◽  
Kazutoshi Takahashi

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.


2019 ◽  
Author(s):  
Sean K. Ryan ◽  
Michael V. Gonzalez ◽  
James P. Garifallou ◽  
Frederick C. Bennett ◽  
Kimberly S. Williams ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document