Sara B. Linker
Salk Institute for Biological Studies
PromoterGeneRNA-SeqInduced pluripotent stem cellInternal medicinePhenotypeMobile genetic elementsEndocrinologySomatic cellDNA repairNeural stem cellGenomeHippocampal formationGene expressionTranscriptomeSet (psychology)Regulation of gene expressionNeuroscienceGenome instabilityCell typeHuman genomeAutismBipolar disorderDentate gyrusSingle-cell analysisHuman brainBonoboAutism spectrum disorderLithium (medication)Context (language use)ExtramuralHippocampusPostmortem brainPersonalized medicineTranscription (biology)Computer scienceHuman geneticsNeurogenesisTransposable elementMutationGeneticsBioinformaticsRetrotransposonComputational biologyMedicineDNA replicationEvolutionary biologyChromatinTranscription factorBiologyMitosisCell biology
27Publications
10H-index
966Citations
Publications 26
Newest
#1Vera Gorbunova (UR: University of Rochester)H-Index: 54
#2Andrei Seluanov (UR: University of Rochester)H-Index: 51
Last. Anna P. Petrashen (Brown University)H-Index: 4
view all 14 authors...
The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity of retrotransposons, a major subgroup of transposons overall, influences and even promotes ...
Source
#1Dylan A. Reid (Salk Institute for Biological Studies)H-Index: 13
#2Patrick J. Reed (Salk Institute for Biological Studies)H-Index: 2
Last. Fred H. Gage (Salk Institute for Biological Studies)H-Index: 237
view all 22 authors...
Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell-induced neurons shows that, in n...
2 CitationsSource
#1Renata Santos (Salk Institute for Biological Studies)H-Index: 24
#2Sara B. Linker (Salk Institute for Biological Studies)H-Index: 10
Last. Fred H. Gage (Salk Institute for Biological Studies)H-Index: 237
view all 14 authors...
Bipolar disorder (BD) is a psychiatric condition characterized by depressive and manic episodes that affect 2% of the world population. The first-line long-term treatment for mood stabilization is lithium (Li). Induced pluripotent stem cell modeling of BD using hippocampal dentate gyrus-like neurons derived from Li-responsive (LR) and Li-non-responsive (NR) patients previously showed neuronal hyperexcitability. Li treatment reversed hyperexcitability only on the LR neurons. In this study we sear...
4 CitationsSource
#1Sara B. Linker (Salk Institute for Biological Studies)H-Index: 10
#2Lynne Randolph-Moore (Salk Institute for Biological Studies)H-Index: 7
Last. Fred H. Gage (Salk Institute for Biological Studies)H-Index: 237
view all 7 authors...
Currently, researchers rely on generalized methods to quantify transposable element (TE) RNA expression, such as RT-qPCR and RNA-seq, that do not distinguish between TEs expressed from their own promoter (bona fide) and TEs that are transcribed from a neighboring gene promoter such as within an intron or exon. This distinction is important owing to the differing functional roles of TEs depending on whether they are independently transcribed. Here we report a simple strategy to examine bona fide ...
2 CitationsSource
#1Sara B. Linker (Salk Institute for Biological Studies)H-Index: 10
#2Ana P.D. Mendes (Salk Institute for Biological Studies)H-Index: 6
Last. Maria C. Marchetto (UCSD: University of California, San Diego)H-Index: 47
view all 3 authors...
BACKGROUND Research evidence accumulated in the past years in both rodent and human models for autism spectrum disorders (ASD) have established insulin-like growth factor 1 (IGF-1) as one of the most promising ASD therapeutic interventions to date. ASD is phenotypically and etiologically heterogeneous, making it challenging to uncover the underlying genetic and cellular pathophysiology of the condition; and to efficiently design drugs with widespread clinical benefits. While IGF-1 effects have b...
3 CitationsSource
#1Krishna C. Vadodaria (Salk Institute for Biological Studies)H-Index: 19
#2Jeffrey R. Jones (Salk Institute for Biological Studies)H-Index: 1
Last. Fred H. Gage (Salk Institute for Biological Studies)H-Index: 237
view all 4 authors...
Brain disorders, from neurodegenerative to psychiatric disorders, are among the most challenging conditions to study because of the intricate nature of the human brain and the limitations of existing model systems in recapitulating all these intricacies. However, innovations in stem cell technologies now allow us to reprogram patient somatic cells to induced pluripotent stem cells (iPSCs), which can then be differentiated to disease-relevant neural and glial cells. iPSCs are a valuable tool to m...
5 CitationsSource
#1Wendy Wenderski (Stanford University)H-Index: 5
#2Lu Wang (UCSD: University of California, San Diego)H-Index: 4
Last. Joseph G. Gleeson (UCSD: University of California, San Diego)H-Index: 91
view all 29 authors...
Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such "early activation" genes silent have been a mystery. In the course of investigating Mendelian recessive autism, we identified six families with segregating loss-of-function mutations in the neuronal BAF (nBAF) subunit ACT...
7 CitationsSource
#1Dylan A. Reid (Salk Institute for Biological Studies)H-Index: 13
#2Patrick J. Reed (Salk Institute for Biological Studies)H-Index: 2
Last. Fred H. Gage (Salk Institute for Biological Studies)H-Index: 237
view all 19 authors...
Neurons are the longest-living cells in our bodies, becoming post-mitotic in early development upon terminal differentiation. Their lack of DNA replication makes them reliant on DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, potentially giving rise to genomic dysfunction that may influence cognitive decline and neurodegenerative diseases. Despite this challenge, our knowledge of how genome instability emerges and what mechanisms neurons and other lon...
1 CitationsSource
#1Wei Shen (McGovern Institute for Brain Research)H-Index: 2
#2Qiu-Wen Wang (THU: Tsinghua University)H-Index: 2
Last. Jun Yao (THU: Tsinghua University)H-Index: 19
view all 22 authors...
The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the ...
3 CitationsSource
#1Debha Amatya (UCSD: University of California, San Diego)H-Index: 5
#2Sara B. Linker (Salk Institute for Biological Studies)H-Index: 10
Last. Yeni Kim (Salk Institute for Biological Studies)H-Index: 3
view all 11 authors...
Summary Neuronal activity can be modeled as a nonlinear dynamical system to yield measures of neuronal state and dysfunction. The electrical recordings of stem cell-derived neurons from individuals with autism spectrum disorder (ASD) and controls were analyzed using minimum embedding dimension (MED) analysis to characterize their dynamical complexity. MED analysis revealed a significant reduction in dynamical complexity in ASD neurons during differentiation, which was correlated to bursting and ...
4 CitationsSource