Now showing items 1-20 of 29

    • ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP 

      Sun, Shuying; Ling, Shuo-Chien; Qiu, Jinsong; Albuquerque, Claudio P.; Zhou, Yu; Tokunaga, Seiya; Li, Hairi; Qiu, Haiyan; Bui, Anh; Yeo, Gene W.; Huang, Eric J.; Eggan, Kevin; Zhou, Huilin; Fu, Xiang-Dong; Lagier-Tourenne, Clotilde; Cleveland, Don W. (2015)
      The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease ALS, is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to ...
    • Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor Neurons 

      Son, Esther Y.; Ichida, Justin K.; Wainger, Brian J.; Toma, Jeremy S.; Rafuse, Victor F.; Woolf, Clifford J.; Eggan, Kevin Carl (Elsevier BV, 2011)
      The mammalian nervous system is composed of a multitude of distinct neuronal subtypes, each with its own phenotype and differential sensitivity to degenerative disease. Although specific neuronal types can be isolated from ...
    • Developing Human Stem Cell Derived Motor Neuron Models of Amyotrophic Lateral Sclerosis 

      Sandoe, Jackson L (2014-10-21)
      Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Amyotrophic ...
    • Developmental Bias in Cleavage-Stage Mouse Blastomeres 

      Tabansky, Inna; Lenarcic, Alan; Draft, Ryan Wesley; Loulier, Karine; Keskin, Derin Benerci; Rosains, Jacqueline; Rivera-Feliciano, Jose; Lichtman, Jeff; Livet, Jean; Stern, Joel N H; Sanes, Joshua R.; Eggan, Kevin Carl (Elsevier BV, 2013)
      BACKGROUND: The cleavage-stage mouse embryo is composed of superficially equivalent blastomeres that will generate both the embryonic inner cell mass (ICM) and the supportive trophectoderm (TE). However, it remains unsettled ...
    • Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human 

      Zhang, Kun; Li, Jin Billy; Gao, Yuan; Egli, Dieter; Xie, Bin; Deng, Jie; Li, Zhe; Lee, Je-Hyuk; Aach, John Dennis; Leproust, Emily M; Eggan, Kevin Carl; Church, George McDonald (Nature Publishing Group, 2009)
      We developed a digital RNA allelotyping method for quantitatively interrogating allele-specific gene expression. This method involves ultra-deep sequencing of padlock captured SNPs from the transcriptome. We characterized ...
    • DNA methylation dynamics of the human preimplantation embryo 

      Smith, Zachary D.; Chan, Michelle M.; Humm, Kathryn C.; Karnik, Rahul; Mekhoubad, Shila; Regev, Aviv; Eggan, Kevin; Meissner, Alexander (2014)
      In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors1-3. This comparatively ...
    • Erosion of Dosage Compensation Impacts Human iPSC Disease Modeling 

      Mekhoubad, Shila; Bock, Christoph; de Boer, A. Sophie; Kiskinis, Evangelos; Meissner, Alexander; Eggan, Kevin Carl (Elsevier BV, 2012)
      Although distinct human induced pluripotent stem cell (hiPSC) lines can display considerable epigenetic variation, it has been unclear whether such variability impacts their utility for disease modeling. Here, we show that ...
    • Exploring the Plasticity of Cellular Fate Using Defined-Factor Reprogramming 

      Son, Yesde (2012-11-02)
      Cellular fate, once established, is usually stable for the lifetime of the cell. However, the mechanisms that restrict the developmental potential of differentiated cells are in principle reversible, as demonstrated by the ...
    • FUS is sequestered in nuclear aggregates in ALS patient fibroblasts 

      Schwartz, Jacob C.; Podell, Elaine R.; Han, Steve S. W.; Berry, James D.; Eggan, Kevin C.; Cech, Thomas R. (The American Society for Cell Biology, 2014)
      Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigate whether mutant FUS protein in ALS patient–derived fibroblasts affects ...
    • Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations 

      Merkle, Florian Tobias; Ghosh, Sulagna; Kamitaki, Nolan; Mitchell, Jana Marie; Avior, Yishai; Mello, Curtis Jay; Kashin, Seva; Mekhoubad, Shila; Ilic, Dusko; Sweetnam, Maura Charlton; Saphier Belfer, Genevieve C; Handsaker, Robert E; Genovese, Giulio; Bar, Shiran; Benvenisty, Nissim; McCarroll, Steven A.; Eggan, Kevin Carl (Springer Nature, 2017)
      Background: Depressive disorders are the second-leading cause of global disability, and an area of increasing focus in international health efforts. We describe a community health worker (CHW) program rolled out in a ...
    • Impracticality of Egg Donor Recruitment in the Absence of Compensation 

      Egli, Dieter; Chen, Alice E.; Saphier, Genevieve; Powers, Douglas; Alper, Michael Myron; Katz, Karin; Berger, Brian Max; Goland, Robin; Leibel, Rudolph L.; Melton, Douglas A.; Eggan, Kevin Carl (Elsevier BV, 2011)
      Unfertilized oocytes of many mammalian species can reprogram somatic cells to a pluripotent state. Human oocytes might therefore be useful for producing patient-derived pluripotent stem cells. Because they would carry the ...
    • Improving Stem Cell-Based Therapy and Developing a Novel Gene Therapy Approach for Treating Duchenne Muscular Dystrophy (DMD) 

      Tabebordbar, Mohammadsharif (2016-01-26)
      Genetic mutations in muscle structural genes can compromise myofiber integrity, causing repeated muscle damage that ultimately exhausts muscle regenerative capacity and results in devastating degenerative conditions such ...
    • Manipulating Somatic Cells to Remove Barriers in Induced Pluripotent Stem Cell Reprogramming 

      Chung, Julia (2013-10-08)
      Development leads unidirectionally towards a more restricted cell fate that is usually stable. However, it has been proven that developmental systems are reversible by the success of animal cloning of a differentiated ...
    • Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts 

      Wainger, Brian J.; Buttermore, Elizabeth D.; Oliveira, Julia T.; Mellin, Cassidy; Lee, Seungkyu; Saber, Wardiya Afshar; Wang, Amy; Ichida, Justin K.; Chiu, Isaac M.; Barrett, Lee; Huebner, Eric A.; Bilgin, Canan; Tsujimoto, Naomi; Brenneis, Christian; Kapur, Kush; Rubin, Lee L.; Eggan, Kevin; Woolf, Clifford J. (2015)
      Reprogramming somatic cells from one cell fate to another can generate specific neurons suitable for disease modeling. To maximize the utility of patient-derived neurons, they must model not only disease-relevant cell ...
    • Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging 

      Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin (Nature Publishing Group, 2016)
      The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) ...
    • The mouse C9ORF72 ortholog is enriched in neurons known to degenerate in ALS and FTD 

      Suzuki, Naoki; Maroof, Asif; Merkle, Florian T; Koszka, Kathryn; Intoh, Atsushi; Armstrong, Ian; Moccia, Rob; Davis-Dusenbery, Brandi N; Eggan, Kevin (2014)
      Using transgenic animals harboring a targeted LacZ insertion, we studied the expression pattern of the C9ORF72 mouse ortholog. Unlike most genes mutated in ALS, which are ubiquitously expressed, the C9ORF72-ortholog was ...
    • Nanog-Independent Reprogramming to iPSCs with Canonical Factors 

      Carter, Ava C.; Davis-Dusenbery, Brandi N.; Koszka, Kathryn; Ichida, Justin K.; Eggan, Kevin (Elsevier, 2014)
      Summary It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem cells and induced pluripotent stem cells (iPSCs). However, ...
    • Notch Inhibition Allows Oncogene-Independent Generation of iPS Cells 

      Ichida, Justin K.; TCW, Julia; Williams Gonzalez, Luis Alberto; Carter, Ava; Shi, Yingxiao; Moura, Marcelo T.; Ziller, Michael Johannes; Singh, Sean; Amabile, Giovanni; Bock, Christoph; Umezawa, Akihiro; Rubin, Lee; Bradner, James Elliott; Akutsu, Hidenori; Meissner, Alexander; Eggan, Kevin Carl (Nature Publishing Group, 2014)
      The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially ...
    • Optimal Timing of Inner Cell Mass Isolation Increases the Efficiency of Human Embryonic Stem Cell Derivation and Allows Generation of Sibling Cell Lines 

      Chen, Alice E.; Egli, Dieter; Niakan, Kathy; Deng, Jie; Akutsu, Hidenori; Yamaki, Mariko; Cowan, Chad; Fitz-Gerald, Claire; Zhang, Kun; Melton, Douglas A.; Eggan, Kevin; Chen, Alice E.; Egli, Dieter; Niakan, Kathy; Deng, Jie; Akutsu, Hidenori; Yamaki, Mariko; Cowan, Chad A.; Fitz-Gerald, Claire; Zhang, Kun; Melton, Douglas A.; Eggan, Kevin Carl (Elsevier, 2009)
    • Pathways Disrupted in Human ALS Motor Neurons Identified through Genetic Correction of Mutant SOD1 

      Kiskinis, Evangelos; Sandoe, Jackson L; Williams, Lauren N.; Boulting, Gabriella Lutz; Moccia, Robert; Wainger, Brian Jason; Han, Steve Sang-woo; Peng, Theodore; Thams, Sebastian; Mikkilineni, Shravani; Mellin, Cassidy; Merkle, Florian Tobias; Davis-Dusenbery, B; Ziller, Michael Johannes; Oakley, Derek Hayden; Ichida, Justin; Di Costanzo, Stefania; Atwater, Nick; Maeder, M; Goodwin, Marcus; Nemesh, James; Handsaker, Robert E; Paull, Daniel; Noggle, Scott; McCarroll, Steven A.; Joung, Jae Keith; Woolf, Carl; Brown, Robert H; Eggan, Kevin Carl (Elsevier BV, 2014)
      Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the ...