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349 results on '"Mikkelsen, Tarjei S"'

1. Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing

Author

Replogle, Joseph M, Norman, Thomas M, Xu, Albert, Hussmann, Jeffrey A, Chen, Jin, Cogan, J Zachery, Meer, Elliott J, Terry, Jessica M, Riordan, Daniel P, Srinivas, Niranjan, Fiddes, Ian T, Arthur, Joseph G, Alvarado, Luigi J, Pfeiffer, Katherine A, Mikkelsen, Tarjei S, Weissman, Jonathan S, and Adamson, Britt

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Genetics, Biological Sciences, Human Genome, Biotechnology, Prevention, Generic health relevance, CRISPR-Cas Systems, Gene Expression Regulation, Gene Targeting, HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Nucleic Acid Amplification Techniques, RNA, Guide, Kinetoplastida, Single-Cell Analysis, Transcriptome
Abstract

Single-cell CRISPR screens enable the exploration of mammalian gene function and genetic regulatory networks. However, use of this technology has been limited by reliance on indirect indexing of single-guide RNAs (sgRNAs). Here we present direct-capture Perturb-seq, a versatile screening approach in which expressed sgRNAs are sequenced alongside single-cell transcriptomes. Direct-capture Perturb-seq enables detection of multiple distinct sgRNA sequences from individual cells and thus allows pooled single-cell CRISPR screens to be easily paired with combinatorial perturbation libraries that contain dual-guide expression vectors. We demonstrate the utility of this approach for high-throughput investigations of genetic interactions and, leveraging this ability, dissect epistatic interactions between cholesterol biogenesis and DNA repair. Using direct capture Perturb-seq, we also show that targeting individual genes with multiple sgRNAs per cell improves efficacy of CRISPR interference and activation, facilitating the use of compact, highly active CRISPR libraries for single-cell screens. Last, we show that hybridization-based target enrichment permits sensitive, specific sequencing of informative transcripts from single-cell RNA-seq experiments.

Published
2020

2. Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity

Author

Yan, Kelley S, Gevaert, Olivier, Zheng, Grace XY, Anchang, Benedict, Probert, Christopher S, Larkin, Kathryn A, Davies, Paige S, Cheng, Zhuan-fen, Kaddis, John S, Han, Arnold, Roelf, Kelly, Calderon, Ruben I, Cynn, Esther, Hu, Xiaoyi, Mandleywala, Komal, Wilhelmy, Julie, Grimes, Sue M, Corney, David C, Boutet, Stéphane C, Terry, Jessica M, Belgrader, Phillip, Ziraldo, Solongo B, Mikkelsen, Tarjei S, Wang, Fengchao, von Furstenberg, Richard J, Smith, Nicholas R, Chandrakesan, Parthasarathy, May, Randal, Chrissy, Mary Ann S, Jain, Rajan, Cartwright, Christine A, Niland, Joyce C, Hong, Young-Kwon, Carrington, Jill, Breault, David T, Epstein, Jonathan, Houchen, Courtney W, Lynch, John P, Martin, Martin G, Plevritis, Sylvia K, Curtis, Christina, Ji, Hanlee P, Li, Linheng, Henning, Susan J, Wong, Melissa H, and Kuo, Calvin J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Digestive Diseases, 1.1 Normal biological development and functioning, Underpinning research, Animals, Antigens, Differentiation, Enteroendocrine Cells, Gene Expression Regulation, Intestinal Mucosa, Jejunum, Mice, Mice, Transgenic, Stem Cells, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5+ ISCs, the most well-defined ISC pool, but Bmi1-GFP+ cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP+ cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1+ cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP+ cells, one of which resembled mature EE cells while the other displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprises a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness.

Published
2017

3. Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions

Author

Ernst, Jason, Melnikov, Alexandre, Zhang, Xiaolan, Wang, Li, Rogov, Peter, Mikkelsen, Tarjei S, and Kellis, Manolis

Subjects
Biological Sciences, Genetics, Chromosome Mapping, Conserved Sequence, Epigenetic Repression, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Nucleotides, Regulatory Sequences, Nucleic Acid, Reproducibility of Results, Sensitivity and Specificity
Abstract

Massively parallel reporter assays (MPRAs) enable nucleotide-resolution dissection of transcriptional regulatory regions, such as enhancers, but only few regions at a time. Here we present a combined experimental and computational approach, Systematic high-resolution activation and repression profiling with reporter tiling using MPRA (Sharpr-MPRA), that allows high-resolution analysis of thousands of regions simultaneously. Sharpr-MPRA combines dense tiling of overlapping MPRA constructs with a probabilistic graphical model to recognize functional regulatory nucleotides, and to distinguish activating and repressive nucleotides, using their inferred contribution to reporter gene expression. We used Sharpr-MPRA to test 4.6 million nucleotides spanning 15,000 putative regulatory regions tiled at 5-nucleotide resolution in two human cell types. Our results recovered known cell-type-specific regulatory motifs and evolutionarily conserved nucleotides, and distinguished known activating and repressive motifs. Our results also showed that endogenous chromatin state and DNA accessibility are both predictive of regulatory function in reporter assays, identified retroviral elements with activating roles, and uncovered 'attenuator' motifs with repressive roles in active chromatin.

Published
2016

4. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids

Author

Salahudeen, Ameen A., Choi, Shannon S., Rustagi, Arjun, Zhu, Junjie, van Unen, Vincent, de la O, Sean M., Flynn, Ryan A., Margalef-Català, Mar, Santos, António J. M., Ju, Jihang, Batish, Arpit, Usui, Tatsuya, Zheng, Grace X. Y., Edwards, Caitlin E., Wagar, Lisa E., Luca, Vincent, Anchang, Benedict, Nagendran, Monica, Nguyen, Khanh, Hart, Daniel J., Terry, Jessica M., Belgrader, Phillip, Ziraldo, Solongo B., Mikkelsen, Tarjei S., Harbury, Pehr B., Glenn, Jeffrey S., Garcia, K. Christopher, Davis, Mark M., Baric, Ralph S., Sabatti, Chiara, Amieva, Manuel R., Blish, Catherine A., Desai, Tushar J., and Kuo, Calvin J.

Published
2020
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5. Mapping and analysis of chromatin state dynamics in nine human cell types

Author

Ernst, Jason, Kheradpour, Pouya, Mikkelsen, Tarjei S, Shoresh, Noam, Ward, Lucas D, Epstein, Charles B, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael, Ku, Manching, Durham, Timothy, Kellis, Manolis, and Bernstein, Bradley E

Subjects
Genetics, Biotechnology, Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Binding Sites, Cell Line, Cell Line, Tumor, Cell Physiological Phenomena, Cells, Cultured, Chromatin, Chromosome Mapping, Gene Expression Regulation, Genome, Human, Hep G2 Cells, Humans, Promoter Regions, Genetic, Reproducibility of Results, Transcription Factors, General Science & Technology
Abstract

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.

Published
2011

7. Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains

Author

Ku, Manching, Koche, Richard P, Rheinbay, Esther, Mendenhall, Eric M, Endoh, Mitsuhiro, Mikkelsen, Tarjei S, Presser, Aviva, Nusbaum, Chad, Xie, Xiaohui, Chi, Andrew S, Adli, Mazhar, Kasif, Simon, Ptaszek, Leon M, Cowan, Chad A, Lander, Eric S, Koseki, Haruhiko, and Bernstein, Bradley E

Subjects
embryonic stem-cells, group proteins ring1a/b, rna-polymerase-ii, nf-kappa-b, developmental regulators, drosophila-melanogaster, polycomb targets, histone h2a, gene family, es cells
Abstract

In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes-the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells.

Published
2008

10. Dissecting neural differentiation regulatory networks through epigenetic footprinting

Author

Ziller, Michael J., Edri, Reuven, Yaffe, Yakey, Donaghey, Julie, Pop, Ramona, Mallard, William, Issner, Robbyn, Gifford, Casey A., Goren, Alon, Xing, Jeffrey, Gu, Hongcang, Cacchiarelli, Davide, Tsankov, Alexander M., Epstein, Charles, Rinn, John L., Mikkelsen, Tarjei S., Kohlbacher, Oliver, Gnirke, Andreas, Bernstein, Bradley E., Elkabetz, Yechiel, and Meissner, Alexander

Subjects
Neural circuitry -- Research, Genetic research, Stem cells -- Genetic aspects, Neurological research, Cell differentiation -- Research, Epigenetic inheritance -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Models derived from human pluripotent stem cells that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signalling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells in the embryonic and adult nervous system (1-3). Here we report the transcriptional and epigenomic analysis of six consecutive neural progenitor cell stages derived from a HES5::eGFP reporter human embryonic stem cell line (4). Using this system, we aimed to model cell-fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell-state transition based on the progressive remodelling of the epigenetic landscape and then validated these through a pooled short hairpin RNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and suggest here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation., We used the human embryonic stem (ES) cell line WA9 (also known as H9) expressing GFP under the HES5 promoter (4) to isolate defined neural progenitor populations of neuroepithelial (NE), [...]

Published
2015

11. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research., Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...]

Published
2012
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12. A unique regulatory phase of DNA methylation in the early mammalian embryo

Author

Smith, Zachary D., Chan, Michelle M., Mikkelsen, Tarjei S., Gu, Hongcang, Gnirke, Andreas, Regev, Aviv, and Meissner, Alexander

Subjects
Methylation -- Genetic aspects -- Physiological aspects, Embryonic development -- Genetic aspects, Molecular biology -- Research, Mammals -- Physiological aspects -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)--including many CpG island promoters--that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern., Cytosine methylation in mammals is an epigenetic modification that is largely restricted to CpG dinucleotides and serves multiple critical functions, including stable repression of target promoters, maintaining genomic integrity, establishing [...]

Published
2012
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13. Comparative Epigenomic Analysis of Murine and Human Adipogenesis

Author

Mikkelsen, Tarjei S., Xu, Zhao, Zhang, Xiaolan, Wang, Li, Gimble, Jeffrey M., Lander, Eric S., and Rosen, Evan D.

Subjects
Stem cells -- Comparative analysis, Genomics -- Comparative analysis, Chromatin -- Comparative analysis, Gene expression -- Comparative analysis, Biological apparatus and supplies -- Comparative analysis, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.09.006 Byline: Tarjei S. Mikkelsen (1), Zhao Xu (1)(2), Xiaolan Zhang (1), Li Wang (1), Jeffrey M. Gimble (3), Eric S. Lander (1), Evan D. Rosen (1)(2) Abstract: We report the generation and comparative analysis of genome-wide chromatin state maps, PPAR[gamma] and CTCF localization maps, and gene expression profiles from murine and human models of adipogenesis. The data provide high-resolution views of chromatin remodeling during cellular differentiation and allow identification of thousands of putative preadipocyte- and adipocyte-specific cis-regulatory elements based on dynamic chromatin signatures. We find that the specific locations of most such elements differ between the two models, including at orthologous loci with similar expression patterns. Based on sequence analysis and reporter assays, we show that these differences are determined, in part, by evolutionary turnover of transcription factor motifs in the genome sequences and that this turnover may be facilitated by the presence of multiple distal regulatory elements at adipogenesis-dependent loci. We also utilize the close relationship between open chromatin marks and transcription factor motifs to identify and validate PLZF and SRF as regulators of adipogenesis. Author Affiliation: (1) Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA (2) Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA (3) Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA Article History: Received 17 April 2010; Revised 13 July 2010; Accepted 27 August 2010 Article Note: (miscellaneous) Published: September 30, 2010

Published
2010

15. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

Author

Guttman, Mitchell, Amit, Ido, Garber, Manuel, French, Courtney, Lin, Michael F., Feldser, David, Huarte, Maite, Zuk, Or, Carey, Bryce W., Cassady, John P., Cabili, Moran N., Jaenisch, Rudolf, Mikkelsen, Tarjei S., Jacks, Tyler, Hacohen, Nir, Bernstein, Bradley E., Kellis, Manolis, Regev, Aviv, Rinn, John L., and Lander, Eric S.

Subjects
Chromatin -- Genetic aspects -- Physiological aspects, Genetic code -- Identification and classification -- Physiological aspects -- Genetic aspects, RNA -- Identification and classification -- Physiological aspects -- Genetic aspects, Mammals -- Genetic aspects -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Identification and classification, Physiological aspects, Genetic aspects
Abstract

There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts (1-4). However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (.95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise (5,6). Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified ~1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes fromembryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFκB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes., There are at present only about a dozen well-characterized lincRNAs in mammals, with transcript sizes ranging from 2.3 to 17.2 kilobases (kb) (7,8). These lincRNAs have distinctive biological roles through [...]

Published
2009

19. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

Author

Yan, Kelley S., Janda, Claudia Y., Chang, Junlei, Zheng, Grace X. Y., Larkin, Kathryn A., Luca, Vincent C., Chia, Luis A., Mah, Amanda T., Han, Arnold, Terry, Jessica M., Ootani, Akifumi, Roelf, Kelly, Lee, Mark, Yuan, Jenny, Li, Xiao, Bolen, Christopher R., Wilhelmy, Julie, Davies, Paige S., Ueno, Hiroo, von Furstenberg, Richard J., Belgrader, Phillip, Ziraldo, Solongo B., Ordonez, Heather, Henning, Susan J., Wong, Melissa H., Snyder, Michael P., Weissman, Irving L., Hsueh, Aaron J., Mikkelsen, Tarjei S., Garcia, K. Christopher, and Kuo, Calvin J.

Subjects
Ligands (Biochemistry) -- Health aspects, Stem cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Kelley S. Yan [1, 2]; Claudia Y. Janda [3]; Junlei Chang [1]; Grace X. Y. Zheng [4]; Kathryn A. Larkin [1]; Vincent C. Luca [3]; Luis A. Chia [1]; [...]

Published
2017
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20. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

Author

Mikkelsen, Tarjei S., Wakefield, Matthew J., Aken, Bronwen, Amemiya, Chris T., Chang, Jean L., Duke, Shannon, Garber, Manuel, Gentles, Andrew J., Goodstadt, Leo, Heger, Andreas, Jurka, Jerzy, Kamal, Michael, Mauceli, Evan, Searle, Stephen M. J., Sharpe, Ted, Baker, Michelle L., Batzer, Mark A., Benos, Panayiotis V., Belov, Katherine, Clamp, Michele, Cook, April, Cuff, James, Das, Radhika, Davidow, Lance, Deakin, Janine E., Fazzari, Melissa J., Glass, Jacob L., Grabherr, Manfred, Greally, John M., Gu, Wanjun, Hore, Timothy A., Huttley, Gavin A., Kleber, Michael, Jirtle, Randy L., Koina, Edda, Lee, Jeannie T., Mahony, Shaun, Marra, Marco A., Miller, Robert D., Nicholls, Robert D., Oda, Mayumi, Papenfuss, Anthony T., Parra, Zuly E., Pollock, David D., Ray, David A., Schein, Jacqueline E., Speed, Terence P., Thompson, Katherine, VandeBerg, John L., Wade, Claire M., Walker, Jerilyn A., Waters, Paul D., Webber, Caleb, Weidman, Jennifer R., Xie, Xiaohui, Zody, Michael C., Baldwin, Jennifer, Abdouelleil, Amr, Abdulkadir, Jamal, Abebe, Adal, Abera, Brikti, Abreu, Justin, Acer, St Christophe, Aftuck, Lynne, Alexander, Allen, An, Peter, Anderson, Erica, Anderson, Scott, Arachi, Harindra, Azer, Marc, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Berlin, Aaron, Bessette, Daniel, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Bourzgui, Imane, Brown, Adam, Cahill, Patrick, Channer, Sheridon, Cheshatsang, Yama, Chuda, Lisa, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Costello, Maura, D'Aco, Katie, Daza, Riza, De Haan, Georgius, DeGray, Stuart, DeMaso, Christina, Dhargay, Norbu, Dooley, Kimberly, Dooley, Erin, Doricent, Missole, Dorje, Passang, Dorjee, Kunsang, Dupes, Alan, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Fisher, Sheila, Foley, Chelsea D., Franke, Alicia, Friedrich, Dennis, Gadbois, Loryn, Gearin, Gary, Gearin, Christina R., Giannoukos, Georgia, Goode, Tina, Graham, Joseph, Grandbois, Edward, Grewal, Sharleen, Gyaltsen, Kunsang, Hafez, Nabil, Hagos, Birhane, Hall, Jennifer, Henson, Charlotte, Hollinger, Andrew, Honan, Tracey, Huard, Monika D., Hughes, Leanne, Hurhula, Brian, Husby, M. Erii, Kamat, Asha, Kanga, Ben, Kashin, Seva, Khazanovich, Dmitry, Kisner, Peter, Lance, Krista, Lara, Marcia, Lee, William, Lennon, Niall, Letendre, Frances, LeVine, Rosie, Lipovsky, Alex, Liu, Xiaohong, Liu, Jinlei, Liu, Shangtao, Lokyitsang, Tashi, Lokyitsang, Yeshi, Lubonja, Rakela, Lui, Annie, MacDonald, Pen, Magnisalis, Vasilia, Maru, Kebede, Matthews, Charles, McCusker, William, McDonough, Susan, Mehta, Teena, Meldrim, James, Meneus, Louis, Mihai, Oana, Mihalev, Atanas, Mihova, Tanya, Mittelman, Rachel, Mlenga, Valentine, Montmayeur, Anna, Mulrain, Leonidas, Navidi, Adam, Naylor, Jerome, Negash, Tamrat, Nguyen, Thu, Nguyen, Nga, Nicol, Robert, Norbu, Choe, Norbu, Nyima, Novod, Nathaniel, O'Neill, Barry, Osman, Sahal, Markiewicz, Eva, Oyono, Otero L., Patti, Christopher, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Raghuraman, Sujaa, Rege, Filip, Reyes, Rebecca, Rise, Cecil, Rogov, Peter, Ross, Keenan, Ryan, Elizabeth, Settipalli, Sampath, Shea, Terry, Sherpa, Ngawang, Shi, Lu, Shih, Diana, Sparrow, Todd, Spaulding, Jessica, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Strader, Christopher, Tesfaye, Senait, Thomson, Talene, Thoulutsang, Yama, Thoulutsang, Dawa, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Young, Geneva, Yu, Qing, Zembek, Lisa, Zhong, Danni, Zimmer, Andrew, Zwirko, Zac, Jaffe, David B., Alvarez, Pablo, Brockman, Will, Butler, Jonathan, Chin, CheeWhye, Gnerre, Sante, MacCallum, Iain, Graves, Jennifer A. Marshall, Ponting, Chris P., Breen, Matthew, Samollow, Paul B., Lander, Eric S., and Lindblad-Toh, Kerstin

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Tarjei S. Mikkelsen (corresponding author) [1, 2]; Matthew J. Wakefield [3]; Bronwen Aken [4]; Chris T. Amemiya [5]; Jean L. Chang [1]; Shannon Duke [6]; Manuel Garber [1]; Andrew [...]

Published
2007
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21. Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites

Author

Xie, Xiaohui, Mikkelsen, Tarjei S., Gnirke, Andreas, Lindblad-Toh, Kerstin, Kellis, Manolis, and Lander, Eric S.

Subjects
Human genome -- Research, Noncoding DNA -- Research, Science and technology
Abstract

Conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, yet their function remains largely unknown. Experimental evidence suggests that many of these elements play regulatory roles, but little is known about regulatory motifs contained within them. Here we describe a systematic approach to discover and characterize regulatory motifs within mammalian CNEs by searching for long motifs (12-22 nt) with significant enrichment in CNEs and studying their biochemical and genomic properties. Our analysis identifies 233 long motifs (LMs), matching a total of [approximately equal to]60,000 conserved instances across the human genome. These motifs include 16 previously known regulatory elements, such as the histone 3'-UTR motif and the neuron-restrictive silencer element, as well as striking examples of novel functional elements. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode. We show that it is bound by the RFX1 protein and identify thousands of conserved motif instances, suggesting a broad role for the RFX family in gene regulation. A second group of motifs ([LM2.sup.*]) does not match any previously known motif. We demonstrate by biochemical and computational methods that it defines a binding site for the CTCF protein, which is involved in insulator function to limit the spread of gene activation. We identify nearly 15,000 conserved sites that likely serve as insulators, and we show that nearby genes separated by predicted CTCF sites show markedly reduced correlation in gene expression, These sites may thus partition the human genome into domains of expression. comparative genomics | conserved noncoding element

Published
2007

22. DNA sequence and analysis of human chromosome 8

Author

Nusbaum, Chad, Mikkelsen, Tarjei S., Zody, Michael C., Asakawa, Shuichi, Taudien, Stefan, Garber, Manuel, Kodira, Chinnappa D., Schueler, Mary G., Shimizu, Atsushi, Whittaker, Charles A., Chang, Jean L., Cuomo, Christina A., Dewar, Ken, FitzGerald, Michael G., Yang, Xiaoping, Allen, Nicole R., Anderson, Scott, Asakawa, Teruyo, Blechschmidt, Karin, Bloom, Toby, Borowsky, Mark L., Butler, Jonathan, Cook, April, Corum, Benjamin, DeArellano, Kurt, DeCaprio, David, Dooley, Kathleen T., Dorris, III, Lester, Engels, Reinhard, Glockner, Gernot, Hafez, Nabil, Hagopian, Daniel S., Hall, Jennifer L., Ishikawa, Sabine K., Jaffe, David B., Kamat, Asha, Kudoh, Jun, Lehmann, Rudiger, Lokitsang, Tashi, Macdonald, Pendexter, Major, John E., Matthews, Charles D., Mauceli, Evan, Menzel, Uwe, Mihalev, Atanas H., Minoshima, Shinsei, Murayama, Yuji, Naylor, Jerome W., Nicol, Robert, Nguyen, Cindy, O'Leary, Sinead B., O'Neill, Keith, Parker, Stephen C. J., Polley, Andreas, Raymond, Christina K., Reichwald, Kathrin, Rodriguez, Joseph, Sasaki, Takashi, Schilhabel, Markus, Siddiqui, Roman, Smith, Cherylyn L., Sneddon, Tam P., Talamas, Jessica A., Tenzin, Pema, Topham, Kerri, Venkataraman, Vijay, Wen, Gaiping, Yamazaki, Satoru, Young, Sarah K., Zeng, Qiandong, Zimmer, Andrew R., Rosenthal, Andre, Birren, Bruce W., Platzer, Matthias, Shimizu, Nobuyoshi, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Chad Nusbaum (corresponding author) [1]; Tarjei S. Mikkelsen [1]; Michael C. Zody [1]; Shuichi Asakawa [2]; Stefan Taudien [3]; Manuel Garber [1]; Chinnappa D. Kodira [1]; Mary G. Schueler [...]

Published
2006
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23. Genome sequence, comparative analysis and haplotype structure of the domestic dog

Author

Lindblad-Toh, Kerstin, Wade, Claire M., Mikkelsen, Tarjei S., Karlsson, Elinor K., Jaffe, David B., Kamal, Michael, Clamp, Michele, Chang, Jean L., Kulbokas, III, Edward J., Zody, Michael C., Mauceli, Evan, Xie, Xiaohui, Breen, Matthew, Wayne, Robert K., Ostrander, Elaine A., Ponting, Chris P., Galibert, Francis, Smith, Douglas R., deJong, Pieter J., Kirkness, Ewen, Alvarez, Pablo, Biagi, Tara, Brockman, William, Butler, Jonathan, Chin, Chee-Wye, Cook, April, Cuff, James, Daly, Mark J., DeCaprio, David, Gnerre, Sante, Grabherr, Manfred, Kellis, Manolis, Kleber, Michael, Bardeleben, Carolyne, Goodstadt, Leo, Heger, Andreas, Hitte, Christophe, Kim, Lisa, Koepfli, Klaus-Peter, Parker, Heidi G., Pollinger, John P., Searle, Stephen M. J., Sutter, Nathan B., Thomas, Rachael, Webber, Caleb, Baldwin, Jennifer, Abebe, Adal, Abouelleil, Amr, Aftuck, Lynne, Ait-zahra, Mostafa, Aldredge, Tyler, Allen, Nicole, An, Peter, Anderson, Scott, Antoine, Claudel, Arachchi, Harindra, Aslam, Ali, Ayotte, Laura, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Benamara, Mostafa, Berlin, Aaron, Bessette, Daniel, Blitshteyn, Berta, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Brown, Adam, Cahill, Patrick, Calixte, Nadia, Camarata, Jody, Cheshatsang, Yama, Chu, Jeffrey, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Dawoe, Tenzin, Daza, Riza, Decktor, Karin, DeGray, Stuart, Dhargay, Norbu, Dooley, Kimberly, Dooley, Kathleen, Dorje, Passang, Dorjee, Kunsang, Dorris, Lester, Duffey, Noah, Dupes, Alan, Egbiremolen, Osebhajajeme, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Ferreira, Patricia, Fisher, Sheila, FitzGerald, Mike, Foley, Karen, Foley, Chelsea, Franke, Alicia, Friedrich, Dennis, Gage, Diane, Garber, Manuel, Gearin, Gary, Giannoukos, Georgia, Goode, Tina, Goyette, Audra, Graham, Joseph, Grandbois, Edward, Gyaltsen, Kunsang, Hafez, Nabil, Hagopian, Daniel, Hagos, Birhane, Hall, Jennifer, Healy, Claire, Hegarty, Ryan, Honan, Tracey, Horn, Andrea, Houde, Nathan, Hughes, Leanne, Hunnicutt, Leigh, Husby, M., Jester, Benjamin, Jones, Charlien, Kamat, Asha, Kanga, Ben, Kells, Cristyn, Khazanovich, Dmitry, Kieu, Alix Chinh, Kisner, Peter, Kumar, Mayank, Lance, Krista, Landers, Thomas, Lara, Marcia, Lee, William, Leger, Jean-Pierre, Lennon, Niall, Leuper, Lisa, LeVine, Sarah, Liu, Jinlei, Liu, Xiaohong, Lokyitsang, Yeshi, Lokyitsang, Tashi, Lui, Annie, Macdonald, Jan, Major, John, Marabella, Richard, Maru, Kebede, Matthews, Charles, McDonough, Susan, Mehta, Teena, Meldrim, James, Melnikov, Alexandre, Meneus, Louis, Mihalev, Atanas, Mihova, Tanya, Miller, Karen, Mittelman, Rachel, Mlenga, Valentine, Mulrain, Leonidas, Munson, Glen, Navidi, Adam, Naylor, Jerome, Nguyen, Tuyen, Nguyen, Nga, Nguyen, Cindy, Nguyen, Thu, Nicol, Robert, Norbu, Nyima, Norbu, Choe, Novod, Nathaniel, Nyima, Tenchoe, Olandt, Peter, O'Neill, Barry, O'Neill, Keith, Osman, Sahal, Oyono, Lucien, Patti, Christopher, Perrin, Danielle, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Rachupka, Anthony, Raghuraman, Sujaa, Rameau, Rayale, Ray, Verneda, Raymond, Christina, Rege, Filip, Rise, Cecil, Rogers, Julie, Rogov, Peter, Sahalie, Julie, Settipalli, Sampath, Sharpe, Theodore, Shea, Terrance, Sheehan, Mechele, Sherpa, Ngawang, Shi, Jianying, Shih, Diana, Sloan, Jessie, Smith, Cherylyn, Sparrow, Todd, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Stone, Sabrina, Sykes, Sean, Tchuinga, Pierre, Tenzing, Pema, Tesfaye, Senait, Thoulutsang, Dawa, Thoulutsang, Yama, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Venkataraman, Vijay, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Yang, Shuli, Yang, Xiaoping, Young, Geneva, Yu, Qing, Zainoun, Joanne, Zembek, Lisa, Zimmer, Andrew, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Kerstin Lindblad-Toh (corresponding author) [1]; Claire M Wade [1, 2]; Tarjei S. Mikkelsen [1, 3]; Elinor K. Karlsson [1, 4]; David B. Jaffe [1]; Michael Kamal [1]; Michele Clamp [...]

Published
2005
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24. DNA sequence and analysis of human chromosome 18

Author

Nusbaum, Chad, Zody, Michael C., Borowsky, Mark L., Kamal, Michael, Kodira, Chinnappa D., Taylor, Todd D., Whittaker, Charles A., Chang, Jean L., Cuomo, Christina A., Dewar, Ken, FitzGerald, Michael G., Yang, Xiaoping, Abouelleil, Amr, Allen, Nicole R., Anderson, Scott, Bloom, Toby, Bugalter, Boris, Butler, Jonathan, Cook, April, DeCaprio, David, Engels, Reinhard, Garber, Manuel, Gnirke, Andreas, Hafez, Nabil, Hall, Jennifer L., Norman, Catherine Hosage, Itoh, Takehiko, Jaffe, David B., Kuroki, Yoko, Lehoczky, Jessica, Lui, Annie, Macdonald, Pendexter, Mauceli, Evan, Mikkelsen, Tarjei S., Naylor, Jerome W., Nicol, Robert, Nguyen, Cindy, Noguchi, Hideki, O'Leary, Sinead B., Piqani, Bruno, L Smith, Cherylyn, Talamas, Jessica A., Topham, Kerri, Totoki, Yasushi, Toyoda, Atsushi, Wain, Hester M., Young, Sarah K., Zeng, Qiandong, Zimmer, Andrew R., Fujiyama, Asao, Hattori, Masahira, Birren, Bruce W., Sakaki, Yoshiyuki, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Chad Nusbaum (corresponding author) [1]; Michael C. Zody [1]; Mark L. Borowsky [1]; Michael Kamal [1]; Chinnappa D. Kodira [1]; Todd D. Taylor [2]; Charles A. Whittaker [1, 8]; [...]

Published
2005
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25. Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

Author

Salahudeen, Ameen A., primary, Choi, Shannon S., additional, Rustagi, Arjun, additional, Zhu, Junjie, additional, de la O, Sean M., additional, Flynn, Ryan A., additional, Margalef-Català, Mar, additional, Santos, António J. M., additional, Ju, Jihang, additional, Batish, Arpit, additional, van Unen, Vincent, additional, Usui, Tatsuya, additional, Zheng, Grace X.Y., additional, Edwards, Caitlin E., additional, Wagar, Lisa E., additional, Luca, Vincent, additional, Anchang, Benedict, additional, Nagendran, Monica, additional, Nguyen, Khanh, additional, Hart, Daniel J., additional, Terry, Jessica M., additional, Belgrader, Phillip, additional, Ziraldo, Solongo B., additional, Mikkelsen, Tarjei S., additional, Harbury, Pehr B., additional, Glenn, Jeffrey S., additional, Garcia, K. Christopher, additional, Davis, Mark M., additional, Baric, Ralph S., additional, Sabatti, Chiara, additional, Amieva, Manuel R., additional, Blish, Catherine A., additional, Desai, Tushar J., additional, and Kuo, Calvin J., additional

Published
2020
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26. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells

Author

Mikkelsen, Tarjei S., Ku, Manching, Jaffe, David B., Issac, Biju, Lieberman, Erez, Giannoukos, Georgia, Alvarez, Pablo, Brockman, William, Kim, Tae-Kyung, Koche, Richard P., Lee, William, Mendenhall, Eric, O'Donovan, Aisling, Presser, Aviva, Russ, Carsten, Xie, Xiaohui, Meissner, Alexander, Wernig, Marius, Jaenisch, Rudolf, Nusbaum, Chad, Lander, Eric S., and Bernstein, Bradley E.

Published
2007
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27. A Human-Specific Gene in Microglia

Author

Hayakawa, Toshiyuki, Angata, Takashi, Lewis, Amanda L., Mikkelsen, Tarjei S., Varki, Nissi M., and Varki, Ajit

Published
2005

29. Convergent and divergent evolution of genomic imprinting in the marsupial Monodelphis domestica

Author

Das Radhika, Anderson Nathan, Koran MaryEllen I, Weidman Jennifer R, Mikkelsen Tarjei S, Kamal Michael, Murphy Susan K, Linblad-Toh Kerstin, Greally John M, and Jirtle Randy L

Subjects
Genomic imprinting, Marsupials, Eutherians, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin specific monoallelic gene expression. It is postulated to have evolved in placental mammals to modulate intrauterine resource allocation to the offspring. In this study, we determined the imprint status of metatherian orthologues of eutherian imprinted genes. Results L3MBTL and HTR2A were shown to be imprinted in Monodelphis domestica (the gray short-tailed opossum). MEST expressed a monoallelic and a biallelic transcript, as in eutherians. In contrast, IMPACT, COPG2, and PLAGL1 were not imprinted in the opossum. Differentially methylated regions (DMRs) involved in regulating imprinting in eutherians were not found at any of the new imprinted loci in the opossum. Interestingly, a novel DMR was identified in intron 11 of the imprinted IGF2R gene, but this was not conserved in eutherians. The promoter regions of the imprinted genes in the opossum were enriched for the activating histone modification H3 Lysine 4 dimethylation. Conclusions The phenomenon of genomic imprinting is conserved in Therians, but the marked difference in the number and location of imprinted genes and DMRs between metatherians and eutherians indicates that imprinting is not fully conserved between the two Therian infra-classes. The identification of a novel DMR at a non-conserved location as well as the first demonstration of histone modifications at imprinted loci in the opossum suggest that genomic imprinting may have evolved in a common ancestor of these two Therian infra-classes with subsequent divergence of regulatory mechanisms in the two lineages.

Published
2012
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30. Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression

Author

Tsankov, Alexander M., primary, Wadsworth, Marc H., additional, Akopian, Veronika, additional, Charlton, Jocelyn, additional, Allon, Samuel J., additional, Arczewska, Aleksandra, additional, Mead, Benjamin E., additional, Drake, Riley S., additional, Smith, Zachary D., additional, Mikkelsen, Tarjei S., additional, Shalek, Alex K., additional, and Meissner, Alexander, additional

Published
2019
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31. An advancement in single cell genomics allows for T cell population analysis at high resolution

Author

Sukovich, David J, primary, Taylor, Sarah E B, additional, Pfeiffer, Katherine A., additional, Stubbington, Michael J T, additional, Lee, Josephine Y, additional, Sapida, Jerald, additional, Roidan, Daniel P., additional, Barrio, Alvaro Martinez, additional, Walter, Dagmar, additional, Brix, Liselotte, additional, Jacobsen, Kivin, additional, Yeung, Bertrand, additional, Zhao, Xinfang, additional, and Mikkelsen, Tarjei S, additional

Published
2019
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32. Deep characterization of tumor microenvironments using single cell multi-omics analysis

Author

Montesclaros, Luz, primary, Boutet, Stephane C, additional, Taylor, Sarah E B, additional, Stubbington, Michael J T, additional, Giangarra, Valeria, additional, Lau, Julia K, additional, Sapida, Jerald, additional, Ziraldo, Solongo, additional, Pfeiffer, Katherine A., additional, Zheng, Grace, additional, Barrio, Alvaro Martinez, additional, Lee, Josephine Y, additional, Marrs, Samuel, additional, Wu, Kevin, additional, and Mikkelsen, Tarjei S, additional

Published
2019
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33. Scalable and comprehensive characterization of antigen-specific CD8 T cells using multi-omics single cell analysis

Author

Boutet, Stephane C, primary, Walter, Dagmar, additional, Stubbington, Michael J T, additional, Pfeiffer, Katherine A, additional, Lee, Josephine Y, additional, Taylor, Sarah E B, additional, Montesclaros, Luz, additional, Lau, Julia K, additional, Riordan, Daniel P, additional, Barrio, Alvaro Martinez, additional, Brix, Liselotte, additional, Jacobsen, Kivin, additional, Yeung, Bertrand, additional, Zhao, Xinfang, additional, and Mikkelsen, Tarjei S, additional

Published
2019
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34. Identification of Functional Variants in the FAM13A Chronic Obstructive Pulmonary Disease Genome-Wide Association Study Locus by Massively Parallel Reporter Assays

Author

Castaldi, Peter J., primary, Guo, Feng, additional, Qiao, Dandi, additional, Du, Fei, additional, Naing, Zun Zar Chi, additional, Li, Yan, additional, Pham, Betty, additional, Mikkelsen, Tarjei S., additional, Cho, Michael H., additional, Silverman, Edwin K., additional, and Zhou, Xiaobo, additional

Published
2019
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36. Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

Author

Massachusetts Institute of Technology. Department of Biology, Jaenisch, Rudolf, Semrau, Stefan, Goldmann, Johanna E., Soumillon, Magali, Mikkelsen, Tarjei S., van Oudenaarden, Alexander, Massachusetts Institute of Technology. Department of Biology, Jaenisch, Rudolf, Semrau, Stefan, Goldmann, Johanna E., Soumillon, Magali, Mikkelsen, Tarjei S., and van Oudenaarden, Alexander

Abstract

Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues., National Science Foundation (U.S.) (Grant HD 045022), National Institutes of Health (U.S.) (Grant RO1-CA084198)

Published
2018

37. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

Author

Belgrader, Phillip, Ueno, Hiroo, Yuan, Jenny, Henning, Susan J., Lee, Mark, Terry, Jessica M., Wong, Melissa H., Ziraldo, Solongo B., Han, Arnold, Li, Xiao, Larkin, Kathryn A., Luca, Vincent C., Ootani, Akifumi, Von Furstenberg, Richard J., Snyder, Michael P., Ordonez, Heather, Kuo, Calvin J., Weissman, Irving L., Chang, Junlei, Hsueh, Aaron J., Yan, Kelley S., Chia, Luis A., Zheng, Grace X. Y., Wilhelmy, Julie, Roelf, Kelly, Garcia, K. Christopher, Janda, Claudia Y., Mikkelsen, Tarjei S., Davies, Paige S., Bolen, Christopher R., and Mah, Amanda T.

Abstract

The canonical Wnt/β-catenin signaling pathway governs diverse developmental, homeostatic and pathologic processes. Palmitoylated Wnt ligands engage cell surface Frizzled (Fzd) receptors and Lrp5/6 co-receptors enabling β-catenin nuclear translocation and Tcf/Lef-dependent gene transactivation1–3. Mutations in Wnt downstream signaling components have revealed diverse functions presumptively attributed to Wnt ligands themselves, although direct attribution remains elusive, as complicated by redundancy between 19 mammalian Wnts and 10 Fzds1 and Wnt hydrophobicity2,3. For example, individual Wnt ligand mutations have not revealed homeostatic phenotypes in the intestinal epithelium4, an archetypal canonical Wnt pathway-dependent rapidly self-renewing tissue whose regeneration is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs)5–9. R-spondin ligands (Rspo1–4) engage distinct Lgr4-6 and Rnf43/Znrf3 receptor classes10–13, markedly potentiate canonical Wnt/β-catenin signaling and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo8,14–17. However, the interchangeability, functional cooperation and relative contributions of Wnt versus Rspo ligands to in vivo canonical Wnt signaling and ISC biology remain unknown. Here, we deconstructed functional roles of Wnt versus Rspo ligands in the intestinal crypt stem cell niche. We demonstrate that the default fate of Lgr5+ ISCs is lineage commitment, escape from which requires both Rspo and Wnt ligands. However, gain-of-function studies using Rspo versus a novel non-lipidated Wnt analog reveal qualitatively distinct, non-interchangeable roles for these ligands in ISCs. Wnts are insufficient to induce Lgr5+ ISC self-renewal, but rather confer a basal competency by maintaining Rspo receptor expression that enables Rspo to actively drive and specify the extent of stem cell expansion. This functionally non-equivalent yet cooperative interplay between Wnt and Rspo ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precision control of tissue regeneration.

Published
2017
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38. Aligning Single-Cell Developmental and Reprogramming Trajectories Identifies Molecular Determinants of Myogenic Reprogramming Outcome

Author

Cacchiarelli, Davide, primary, Qiu, Xiaojie, additional, Srivatsan, Sanjay, additional, Manfredi, Anna, additional, Ziller, Michael, additional, Overbey, Eliah, additional, Grimaldi, Antonio, additional, Grimsby, Jonna, additional, Pokharel, Prapti, additional, Livak, Kenneth J., additional, Li, Shuqiang, additional, Meissner, Alexander, additional, Mikkelsen, Tarjei S., additional, Rinn, John L., additional, and Trapnell, Cole, additional

Published
2018
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41. Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency

Author

Massachusetts Institute of Technology. Department of Biology, Lander, Eric Steven, Cacchiarelli, Davide, Trapnell, Cole, Ziller, Michael J., Soumillon, Magali, Cesana, Marcella, Karnik, Rahul, Donaghey, Julie, Smith, Zachary D., Ratanasirintrawoot, Sutheera, Zhang, Xiaolan, Ho Sui, Shannan J., Wu, Zhaoting, Akopian, Veronika, Gifford, Casey A., Doench, John, Rinn, John L., Daley, George Q., Meissner, Alexander, Mikkelsen, Tarjei S., Massachusetts Institute of Technology. Department of Biology, Lander, Eric Steven, Cacchiarelli, Davide, Trapnell, Cole, Ziller, Michael J., Soumillon, Magali, Cesana, Marcella, Karnik, Rahul, Donaghey, Julie, Smith, Zachary D., Ratanasirintrawoot, Sutheera, Zhang, Xiaolan, Ho Sui, Shannan J., Wu, Zhaoting, Akopian, Veronika, Gifford, Casey A., Doench, John, Rinn, John L., Daley, George Q., Meissner, Alexander, and Mikkelsen, Tarjei S.

Abstract

Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here, we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies.

Published
2017

42. Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

Author

CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Semrau, Stefan, Goldmann, Johanna E., Soumillon, Magali, Mikkelsen, Tarjei S., Jaenisch, Rudolf, Van Oudenaarden, Alexander, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Semrau, Stefan, Goldmann, Johanna E., Soumillon, Magali, Mikkelsen, Tarjei S., Jaenisch, Rudolf, and Van Oudenaarden, Alexander

Published
2017

43. A distant trophoblast-specific enhancer controls HLA-G expression at the maternal–fetal interface

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Gifford, David K, Ferreira, Leonardo M. R., Meissner, Torsten B., Mikkelsen, Tarjei S., Mallard, William, O’Donnell, Charles W., Tilburgs, Tamara, Gomes, Hannah A. B., Camahort, Raymond, Sherwood, Richard I., Rinn, John L., Cowan, Chad A., Strominger, Jack L., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Gifford, David K, Ferreira, Leonardo M. R., Meissner, Torsten B., Mikkelsen, Tarjei S., Mallard, William, O’Donnell, Charles W., Tilburgs, Tamara, Gomes, Hannah A. B., Camahort, Raymond, Sherwood, Richard I., Rinn, John L., Cowan, Chad A., and Strominger, Jack L.

Abstract

HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L. Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta. RNA-seq analysis demonstrated that Enhancer L specifically controls HLA-G expression. Moreover, DNase-seq and chromatin conformation capture (3C) defined Enhancer L as a cell type-specific enhancer that loops into the HLA-G promoter. Interestingly, MPRA-based saturation mutagenesis of Enhancer L identified motifs for transcription factors of the CEBP and GATA families essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as the mechanism controlling tissue-specific HLA-G expression at the maternal–fetal interface. More broadly, these results establish the combination of MPRA and CRISPR/Cas9 deletion as a powerful strategy to investigate human immune gene regulation.

Published
2017

44. Registry in a tube: multiplexed pools of retrievable parts for genetic design space exploration

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Woodruff, Lauren B, Gordon, David B, Voigt, Christopher A., Gorochowski, Thomas Edward, Nicol, Robert, Roehner, Nicholas, Mikkelsen, Tarjei S., Densmore, Douglas, Massachusetts Institute of Technology. Department of Biological Engineering, Woodruff, Lauren B, Gordon, David B, Voigt, Christopher A., Gorochowski, Thomas Edward, Nicol, Robert, Roehner, Nicholas, Mikkelsen, Tarjei S., and Densmore, Douglas

Abstract

Genetic designs can consist of dozens of genes and hundreds of genetic parts. After evaluating a design, it is desirable to implement changes without the cost and burden of starting the construction process from scratch. Here, we report a two-step process where a large design space is divided into deep pools of composite parts, from which individuals are retrieved and assembled to build a final construct. The pools are built via multiplexed assembly and sequenced using next-generation sequencing. Each pool consists of ∼20 Mb of up to 5000 unique and sequence-verified composite parts that are barcoded for retrieval by PCR. This approach is applied to a 16-gene nitrogen fixation pathway, which is broken into pools containing a total of 55 848 composite parts (71.0 Mb). The pools encompass an enormous design space (1043 possible 23 kb constructs), from which an algorithm-guided 192-member 4.5 Mb library is built. Next, all 1030 possible genetic circuits based on 10 repressors (NOR/NOT gates) are encoded in pools where each repressor is fused to all permutations of input promoters. These demonstrate that multiplexing can be applied to encompass entire design spaces from which individuals can be accessed and evaluated., Institute for Collaborative Biotechnologies (W911NF-09-0001), United States. Office of Naval Research. Multidisciplinary University Research Initiative (N00014-13-1-0074), United States. Defense Advanced Research Projects Agency. Living Foundries Program (Awards HR0011-12-C-0067, HR0011- 13-1-0001, HR0011-15-C-0084 and HR0011-15-C-0084)

Published
2017

45. High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis

Author

Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Regiv, Aviv, Agarwala, Sudeep, Lander, Eric Steven, Fink, Gerald R., Schwartz, Schraga, Mumbach, Maxwell R., Jovanovic, Marko, Mertins, Philipp, Shishkin, Alexander, Tabach, Yuval, Mikkelsen, Tarjei S., Satija, Rahul, Ruvkun, Gary, Carr, Steven A., Regev, Aviv, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Regiv, Aviv, Agarwala, Sudeep, Lander, Eric Steven, Fink, Gerald R., Schwartz, Schraga, Mumbach, Maxwell R., Jovanovic, Marko, Mertins, Philipp, Shishkin, Alexander, Tabach, Yuval, Mikkelsen, Tarjei S., Satija, Rahul, Ruvkun, Gary, Carr, Steven A., and Regev, Aviv

Abstract

N[superscript 6]-methyladenosine (m[superscript 6]A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m[superscript 6]A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification., American Cancer Society (Professor of Genetics), National Institutes of Health (U.S.) (NIH Grant GM035010), National Institutes of Health (U.S.) (NIH Grant U54 HG003067), Broad Institute of MIT and Harvard (Funds), National Human Genome Research Institute (U.S.) (NHGRI Pioneer Award), Howard Hughes Medical Institute, Human Frontier Science Program (Strasbourg, France) (Fellowship)

Published
2017

48. Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Author

Kadoki, Motohiko, primary, Patil, Ashwini, additional, Thaiss, Cornelius C., additional, Brooks, Donald J., additional, Pandey, Surya, additional, Deep, Deeksha, additional, Alvarez, David, additional, von Andrian, Ulrich H., additional, Wagers, Amy J., additional, Nakai, Kenta, additional, Mikkelsen, Tarjei S., additional, Soumillon, Magali, additional, and Chevrier, Nicolas, additional

Published
2017
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49. Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci

Author

Pashos, Evanthia E., primary, Park, YoSon, additional, Wang, Xiao, additional, Raghavan, Avanthi, additional, Yang, Wenli, additional, Abbey, Deepti, additional, Peters, Derek T., additional, Arbelaez, Juan, additional, Hernandez, Mayda, additional, Kuperwasser, Nicolas, additional, Li, Wenjun, additional, Lian, Zhaorui, additional, Liu, Ying, additional, Lv, Wenjian, additional, Lytle-Gabbin, Stacey L., additional, Marchadier, Dawn H., additional, Rogov, Peter, additional, Shi, Jianting, additional, Slovik, Katherine J., additional, Stylianou, Ioannis M., additional, Wang, Li, additional, Yan, Ruilan, additional, Zhang, Xiaolan, additional, Kathiresan, Sekar, additional, Duncan, Stephen A., additional, Mikkelsen, Tarjei S., additional, Morrisey, Edward E., additional, Rader, Daniel J., additional, Brown, Christopher D., additional, and Musunuru, Kiran, additional

Published
2017
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