Samuel Jesuadian

@article{sanchez-luque_line-1_2019,

title = {LINE-1 Evasion of Epigenetic Repression in Humans},

author = {Francisco J Sanchez-Luque and Marie-Jeanne H C Kempen and Patricia Gerdes and Dulce B Vargas-Landin and Sandra R Richardson and Robin-Lee Troskie and Samuel J Jesuadian and Seth W Cheetham and Patricia E Carreira and Carmen Salvador-Palomeque and Marta Garc\'{i}a-Ca\~{n}adas and Martin Mu\~{n}oz-Lopez and Laura Sanchez and Mischa Lundberg and Angela Macia and Sara R Heras and Paul M Brennan and Ryan Lister and Jose L Garcia-Perez and Adam D Ewing and Geoffrey J Faulkner},

url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(19)30396-X},

doi = {10.1016/j.molcel.2019.05.024},

issn = {1097-2765},

year  = {2019},

date = {2019-01-01},

urldate = {2019-06-24},

journal = {Molecular Cell},

volume = {0},

number = {0},

abstract = {textlessh2textgreaterSummarytextless/h2textgreatertextlessptextgreaterEpigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3ʹ transduction. The source (donor) L1 for this insertion was slightly 5ʹ truncated, lacked the YY1 binding site, and was highly mobile when tested textitin vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.textless/ptextgreater},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nguyen_l1_2018,

title = {L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution},

author = {Thu H M Nguyen and Patricia E Carreira and Francisco J Sanchez-Luque and Stephanie N Schauer and Allister C Fagg and Sandra R Richardson and Claire M Davies and Samuel J Jesuadian and Marie-Jeanne H C Kempen and Robin-Lee Troskie and Cini James and Elizabeth A Beaven and Tristan P Wallis and Jermaine I G Coward and Naven P Chetty and Alexander J Crandon and Deon J Venter and Jane E Armes and Lewis C Perrin and John D Hooper and Adam D Ewing and Kyle R Upton and Geoffrey J Faulkner},

url = {http://www.sciencedirect.com/science/article/pii/S2211124718308714},

doi = {10.1016/j.celrep.2018.05.090},

issn = {2211-1247},

year  = {2018},

date = {2018-06-01},

urldate = {2018-08-28},

journal = {Cell Reports},

volume = {23},

number = {13},

pages = {3730--3740},

abstract = {Summary 

LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Richardson2017-hr,

title = {Heritable L1 retrotransposition in the mouse primordial  germline and early embryo},

author = {Sandra R Richardson and Patricia Gerdes and Daniel J Gerhardt and Francisco J Sanchez-Luque and Gabriela-Oana Bodea and Martin Mu{~n}oz-Lopez and Samuel J Jesuadian and Marie-Jeanne H C Kempen and Patricia E Carreira and Jeffrey A Jeddeloh and Jose L Garcia-Perez and Haig H Kazazian Jr and Adam D Ewing and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1101/gr.219022.116},

year  = {2017},

date = {2017-08-01},

journal = {Genome Res.},

volume = {27},

number = {8},

pages = {1395--1405},

abstract = {LINE-1 (L1) retrotransposons are a noted source of genetic 

 diversity and disease in mammals. To expand its genomic 

 footprint, L1 must mobilize in cells that will contribute 

 their genetic material to subsequent generations. Heritable L1 

 insertions may therefore arise in germ cells and in 

 pluripotent embryonic cells, prior to germline specification, 

 yet the frequency and predominant developmental timing of such 

 events remain unclear. Here, we applied mouse retrotransposon 

 capture sequencing (mRC-seq) and whole-genome sequencing (WGS) 

 to pedigrees of C57BL/6J animals, and uncovered an L1 

 insertion rate of $geq$1 event per eight births. We traced 

 heritable L1 insertions to pluripotent embryonic cells and, 

 strikingly, to early primordial germ cells (PGCs). New L1 

 insertions bore structural hallmarks of target-site primed 

 reverse transcription (TPRT) and mobilized efficiently in a 

 cultured cell retrotransposition assay. Together, our results 

 highlight the rate and evolutionary impact of heritable L1 

 retrotransposition and reveal retrotransposition-mediated 

 genomic diversification as a fundamental property of 

 pluripotent embryonic cells in vivo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Upton2015-qu,

title = {Ubiquitous L1 mosaicism in hippocampal neurons},

author = {Kyle R Upton and Daniel J Gerhardt and Samuel J Jesuadian and Sandra R Richardson and Francisco J S\'{a}nchez-Luque and Gabriela O Bodea and Adam D Ewing and Carmen Salvador-Palomeque and Marjo S van der Knaap and Paul M Brennan and Adeline Vanderver and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1016/j.cell.2015.03.026},

year  = {2015},

date = {2015-04-01},

journal = {Cell},

volume = {161},

number = {2},

pages = {228--239},

abstract = {Somatic LINE-1 (L1) retrotransposition during neurogenesis is 

 a potential source of genotypic variation among neurons. As a 

 neurogenic niche, the hippocampus supports pronounced L1 

 activity. However, the basal parameters and biological impact 

 of L1-driven mosaicism remain unclear. Here, we performed 

 single-cell retrotransposon capture sequencing (RC-seq) on 

 individual human hippocampal neurons and glia, as well as 

 cortical neurons. An estimated 13.7 somatic L1 insertions 

 occurred per hippocampal neuron and carried the sequence 

 hallmarks of target-primed reverse transcription. Notably, 

 hippocampal neuron L1 insertions were specifically enriched in 

 transcribed neuronal stem cell enhancers and hippocampus 

 genes, increasing their probability of functional relevance. 

 In addition, bias against intronic L1 insertions sense 

 oriented relative to their host gene was observed, perhaps 

 indicating moderate selection against this configuration in 

 vivo. These experiments demonstrate pervasive L1 mosaicism at 

 genomic loci expressed in hippocampal neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}