The Emergence of Stem Cell‐Based Brain Organoids: Trends and Challenges

Gopalakrishnan, Jay

doi:10.1002/bies.201900011

Cited by 31 publications

(33 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ventricular zone (VZ) harbors proliferating neural progenitors cells (NPCs) that display typically elongated nuclei which align to form a lumen, a neural tube-like structure. Cortical neurons are positioned basally to the VZ, forming a cortical plate ª 2020 The Authors The EMBO Journal 39: (Lancaster & Knoblich, 2014;Giandomenico & Lancaster, 2017;Gopalakrishnan, 2019). We exposed at least two different age groups of organoids (Day-15 and Day-60) to SARS-CoV-2 (TCID50/ml of 50 which is equivalent to 17.5 PFU/organoid, see Materials and Methods section for details) and analyzed after 2 and 4 days post-infection (dpi).…”

Section: Sars-cov-2 Targets Neurons Of Human Brain Organoidsmentioning

confidence: 99%

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

et al. 2020

Self Cite

View full text Add to dashboard Cite

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS-CoV-2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS-CoV-2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS-CoV-2 and emphasize that brain organoids could model CNS pathologies of COVID-19.

show abstract

Section: Sars-cov-2 Targets Neurons Of Human Brain Organoidsmentioning

confidence: 99%

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, apical neural progenitors cells displaying elongated nuclei (NPCs) are aligned to form a lumen that is similar to the ventricular zone (VZ) of the mammalian brain. Cortical neurons are positioned basally to the VZ forming cortical plate (Figure 2A) (23) (24,25). We exposed at least two different age groups of organoids (Day-15 and Day-60) to SARS-CoV-2 (TCID 50 /mL of 50) and analyzed after 2-and 4-dpi.…”

Section: Sars-cov-2 Targets Human Brain Organoids But Does Not Appearmentioning

confidence: 99%

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

Gopalakrishnan

Ramani

Mueller

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19.

show abstract

“…Our approach is applicable to any inherited disease, both WGS and RNA-seq techniques are commercially available, gold standards are being established and the analysis tools are readily accessible 47, 48, 49–55, 81, 82 . Ex vivo organoid models are being developed for a multitude of tissues including brain 83, 84 , kidney 85 , liver 86, 87 and lung 88 .…”

Section: Discussionmentioning

confidence: 99%

A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families

Bronstein

Capowski

Mehrotra

et al. 2019

Preprint

View full text Add to dashboard Cite

Inherited retinal degenerations (IRDs) are at the focus of current genetic therapeutic advancements. For a genetic treatment such as gene therapy to be successful an accurate genetic diagnostic is required. Genetic diagnostics relies on the assessment of the probability that a given DNA variant is pathogenic. Non-coding variants present a unique challenge for such assessments as compared to coding variants. For one, non-coding variants are present at much higher number in the genome than coding variants. In addition, our understanding of the rules that govern the non-coding regions of the genome is less complete than our understanding of the coding regions. Methods that allow for both the identification of candidate non-coding pathogenic variants and their functional validation may help overcome these caveats allowing for a greater number of patients to benefit from advancements in genetic therapeutics. We present here an unbiased approach combining whole genome sequencing (WGS) with patient induced pluripotent stem cell (iPSC) derived retinal organoids (ROs) transcriptome analysis. With this approach we identified and functionally validated a novel pathogenic non-coding variant in a small family with a previously unresolved genetic diagnosis.

show abstract

The Emergence of Stem Cell‐Based Brain Organoids: Trends and Challenges

Cited by 31 publications

References 67 publications

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families

Contact Info

Product

Resources

About