Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts

Vermilyea, Scott C.; Guthrie, Scott; Meyer, Michaël; Smuga-Otto, Kim; Braun, Katarina M.; Howden, Sara E.; Thomson, James A.; Zhang, Su‐Chun; Emborg, Marina E.; Golos, Thaddeus G.

doi:10.1089/scd.2017.0069

Cited by 30 publications

(28 citation statements)

References 17 publications

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“…Instead of aspirating the Accutase before adding PBS to fully dissociate the cells, DMEM/F12 media was added directly to the Accutase to wash the cells and then spun down to remove the Accutase/media mixture. The cj367 ESCs were also confirmed to be pluripotent by immunostaining for pluripotency markers NANOG, SSEA4, and OCT3/4 (Figure 1d-f) as was initially demonstrated elsewhere (Vermilyea et al 2017).…”

Section: Resultssupporting

confidence: 68%

“…Several marmoset embryonic stem cell (ESC) lines and induced pluripotent stem cell (iPSC) lines with the capabilities of differentiating into specified cell lineages are now available (Thomson et al 1996; Sasaki et al 2005; Tomioka et al 2010; Vermilyea et al 2017). The first transgenic primate showing successful germline transmission of transgenes was accomplished using the marmoset in which lentiviruses expressing enhanced green fluorescent protein (EGFP) were injected into preimplantation embryos (Sasaki et al 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Here, we performed whole-genome characterization in a haplotype-resolved manner for marmoset ESC line cj367 from the Wisconsin National Primate Research Center (Vermilyea et al 2017). To the best of our knowledge, this is the first haplotype-resolved analysis of a marmoset genome and the first whole-genome characterization of any marmoset ESC line.…”

Section: Introductionmentioning

confidence: 99%

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Haplotype-phased common marmoset embryonic stem cells for genome editing using CRISPR/Cas9

Zhou

Leung

Ward

et al. 2018

Preprint

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Due to anatomical and physiological similarities to humans, the common marmoset (Callithrix jacchus) is an ideal organism for the study human diseases. Researchers are currently leveraging genome-editing technologies such as CRISPR/Cas9 to genetically engineer marmosets for the in vivo biomedical modeling of human neuropsychiatric and neurodegenerative diseases. The genome characterization of these cell lines greatly reinforces these transgenic efforts. It also provides the genomic contexts required for the accurate interpretation of functional genomics data. We performed haplotype-resolved whole-genome characterization for marmoset ESC line cj367 from the Wisconsin National Primate Research Center. This is the first haplotype-resolved analysis of a marmoset genome and the first whole-genome characterization of any marmoset ESC line. We identified and phased single-nucleotide variants (SNVs) and Indels across the genome. By leveraging this haplotype information, we then compiled a list of cj367 ESC allele-specific CRISPR targeting sites. Furthermore, we demonstrated successful Cas9 Endonuclease Dead (dCas9) expression and targeted localization in cj367 as well as sustained pluripotency after dCas9 transfection by teratoma assay. Lastly, we show that these ESCs can be directly induced into functional neurons in a rapid, single-step process. Our study provides a valuable set of genomic resources for primate transgenics in this post-genome era.

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Section: Resultssupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Haplotype-phased common marmoset embryonic stem cells for genome editing using CRISPR/Cas9

Zhou

Leung

Ward

et al. 2018

Preprint

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“…With PARK2, there is a posited role of dopaminergic systems in PTSD and epidemiological evidence for association of Parkinson Disease and PTSD. [34][35][36] PODXL is involved in neural development and synapse formation, 37,38 SH3RF3 is associated with neurocognition and dementia, 39,40 and ZDHHC14 is associated with regulation of β -adrenergic receptors. 41,42 Finally, the HLA-B complex may be related through the known role of immunity and inflammation in stress-related disorders.…”

Section: Discussionmentioning

confidence: 99%

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Nievergelt

Klengel

et al. 2018

Preprint

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Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson's Disease gene, PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and major depressive disorder, we show evidence that some of our loci may be specific to PTSD. These results demonstrate the role of genetic variation contributing to the biology of differential risk for PTSD and the necessity of expanding GWAS beyond European ancestry.Comparability of PGC2 studies PGC2 compiled the largest collection of global PTSD GWAS to date, with subjects recruited from both clinically deeply characterized, small patient groups and large cohorts with self-reported PTSD symptoms. We did not restrict the type of trauma subjects were exposed to, and trauma included both civilian and/or military events, often with pre-existing exposure to childhood trauma. To evaluate the comparability of these phenotypically heterogeneous studies we first estimated genetic correlations with LDSC, 15 a method that leverages GWAS summary results, the only data type available to PGC-PTSD for several of the larger military and non-US cohorts. We found significant genetic correlations (r g ) between studies using a cross-validation approach including all PGC2 EUA subjects (10 runs with studies randomly placed into 2 groups; mean r g = 0.56, mean SE = 0.23, mean p = 0.029, Supplementary Table 8).Next, additional analyses on the UK Biobank cohort (UKBB) were performed. This cohort comprises a very large proportion of the data, with almost as many EUA cases as the rest of the EUA PGC2 combined (referred to as PGC1.5). PTSD screening in UKBB was based on self-reported symptoms from a mental health survey. 16 We found a considerable genetic correlation between the UKBB and PGC1.5 EUA subjects (r g = 0.73, SE = 0.21, p = 0.0005; Supplementary Table 9). Further, sensitivity analyses in the UKBB using 3 alternative inclusion criteria for PTSD cases and controls showed stable correlations with PGC1.5 (P1 -P3; r g = 0.72 -0.79; Supplementary Table 10). Subsequent analyses were based on the UKBB phenotype including the largest number of subjects (P1; N = 126,188). Sex-stratified genetic correlations support the findings of a significant genetic signal...

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“…The common marmoset (Callithrix jacchus) is a New World nonhuman primate, originally inhabiting in Brazil, South America, with some populations distributed in Australia and Africa 1 . Due to their small body size, ease of handling, shorter gestation period, and earlier sexual maturation as well as lower maintenance cost compared to Old World nonhuman primates, common marmosets are being used increasingly as one of the mainstream nonhuman primate animal models in biomedical research, including neuroscience, infectious diseases, reproductive biology, stem cell, and toxicological tests [2][3][4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo

et al. 2018

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Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.

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Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts

Cited by 30 publications

References 17 publications

Haplotype-phased common marmoset embryonic stem cells for genome editing using CRISPR/Cas9

Haplotype-phased common marmoset embryonic stem cells for genome editing using CRISPR/Cas9

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo

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