Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936

Toombs, Jamie; Panther, Lindsay; Ornelas, Loren; Liu, Chunyan; Gomez, Emilda; Martín‐Ibáñez, Raquel; Cox, Simon R.; Ritchie, Stuart J.; Harris, Sarah E.; Taylor, Adele M.; Redmond, Paul; Russ, Tom C.; Murphy, Lee; Cooper, James D.; Burr, Karen; Selvaraj, Bhuvaneish T.; Browne, Cathy; Svendsen, Clive N.; Cowley, Sally A.; Deary, Ian J.; Chandran, Siddharthan; Spires‐Jones, Tara L.; Sareen, Dhruv

doi:10.1016/j.scr.2020.101851

Cited by 16 publications

(27 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, blood draws are less invasive and carry lower risk for patients than skin biopsies, which improved the overall risk-benefit ratio for the study. Rigorous quality control (QC) (Supplementary Table 6) was performed on each AALS iPS cell line, similar to previously publications 35 . G-band karyotype was performed at multiple passages for each AALS iPS cell line, which provides confidence about the genetic integrity of the AALS iPS cell repository, given that each iPS cell line is karyotyped at multiple passages.…”

Section: Online Contentmentioning

confidence: 99%

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines

Baxi

Thompson

et al. 2022

Nat Neurosci

Self Cite

View full text Add to dashboard Cite

Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical–molecular–biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition. The iPS spinal neurons were blood derived from each patient and these cells underwent multi-omic analytics including whole-genome sequencing, RNA transcriptomics, ATAC-sequencing and proteomics. The intent of these data is for the generation of integrated clinical and biological signatures using bioinformatics, statistics and computational biology to establish patterns that may lead to a better understanding of the underlying mechanisms of disease, including subgroup identification. A web portal for open-source sharing of all data was developed for widespread community-based data analytics.

show abstract

Section: Online Contentmentioning

confidence: 99%

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines

Baxi

Thompson

et al. 2022

Nat Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…We differentiated five iPSC lines from blood samples of healthy aged people participating in the Lothian Birth Cohort 1936 (LBC1936) study ( Toombs et al., 2020 ). Briefly, peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28 and SV40LT).…”

Section: Methodsmentioning

confidence: 99%

Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer’s disease

Yeap

Sathyaprakash

Toombs

et al. 2022

Brain and Neuroscience Advances

Self Cite

View full text Add to dashboard Cite

Synapse loss is associated with cognitive decline in Alzheimer’s disease, and owing to their plastic nature, synapses are an ideal target for therapeutic intervention. Oligomeric amyloid beta around amyloid plaques is known to contribute to synapse loss in mouse models and is associated with synapse loss in human Alzheimer’s disease brain tissue, but the mechanisms leading from Aβ to synapse loss remain unclear. Recent data suggest that the fast-activating and -inactivating voltage-gated potassium channel subtype 3.4 (Kv3.4) may play a role in Aβ-mediated neurotoxicity. Here, we tested whether this channel could also be involved in Aβ synaptotoxicity. Using adeno-associated virus and clustered regularly interspaced short palindromic repeats technology, we reduced Kv3.4 expression in neurons of the somatosensory cortex of APP/PS1 mice. These mice express human familial Alzheimer’s disease-associated mutations in amyloid precursor protein and presenilin-1 and develop amyloid plaques and plaque-associated synapse loss similar to that observed in Alzheimer’s disease brain. We observe that reducing Kv3.4 levels ameliorates dendritic spine loss and changes spine morphology compared to control virus. In support of translational relevance, Kv3.4 protein was observed in human Alzheimer’s disease and control brain and is associated with synapses in human induced pluripotent stem cell–derived cortical neurons. We also noted morphological changes in induced pluripotent stem cell neurones challenged with human Alzheimer’s disease-derived brain homogenate containing Aβ but, in this in vitro model, total mRNA levels of Kv3.4 were found to be reduced, perhaps as an early compensatory mechanism for Aβ-induced damage. Overall, our results suggest that approaches to reduce Kv3.4 expression and/or function in the Alzheimer’s disease brain could be protective against Aβ-induced synaptic alterations.

show abstract

“…We differentiated five iPSC lines from blood samples of healthy aged people participating in the Lothian Birth Cohort 1936 (LBC1936) study (Toombs et al, 2020). Briefly, peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT).…”

Section: Methodsmentioning

confidence: 99%

Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer’s disease

Yeap

Sathyaprakash²,

Toombs³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Synapse loss is associated with cognitive decline in Alzheimer’s disease (AD) and owing to their plastic nature, synapses are an ideal target for therapeutic intervention. Oligomeric amyloid beta (Aβ) around amyloid plaques is known to contribute to synapse loss in mouse models and is associated with synapse loss in human AD brain tissue, but the mechanisms leading from Aβ to synapse loss remain unclear. Recent data suggest that the fast-activating and -inactivating voltagegated potassium channel subtype 3.4 (Kv3.4) may play a role in Aβ-mediated neurotoxicity. Here, we tested whether this channel could also be involved in Aβ synaptotoxicity. Using adeno-associated virus and CRISPR (clustered regularly interspaced short palindromic repeats) technology, we reduced Kv3.4 expression in neurons of the somatosensory cortex of APP/PS1 mice. These mice express human familial AD associated mutations in amyloid precursor protein and presenilin 1 and develop amyloid plaques and plaque-associated synapse loss similar to that observed in AD brain. We observe that reducing Kv3.4 levels ameliorates dendritic spine loss and changes spine morphology compared to control virus. In support of translational relevance, Kv3.4 protein was observed in human AD and control brain and is associated with synapses in human iPSC-derived cortical neurons. Interestingly, we observe a decrease in Kv3.4 expression in iPSC derived cortical neurons when they are challenged with human Alzheimer’s disease derived brain homogenate. These results suggest that approaches to reduce Kv3.4 expression and/or function could be protective against Aβ-induced synaptic alterations.

show abstract

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936

Cited by 16 publications

References 3 publications

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines

Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer’s disease

Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer’s disease

Contact Info

Product

Resources

About