Yin Shen, PhD

Assistant Professor
Department of Neurology
Institute for Human Genetics

We are a functional genomics lab interested in investigating fundamental mechanisms of transcriptional control underlying cellular function. We utilize human pluripotent stem cells to model development and diseases as well as innovative genomic and genetic tools to investigate how regulatory elements affect gene expression. Specifically, we focus on elucidating the causal relationship between genetic and epigenetic variations in regulatory sequences (e.g., enhancers) in the context of development and diseases, and how these factors interplay to control gene regulation in mammalian cells.

  1. Functional genomics (the ENCODE project): high-throughput CRISPR/Cas9 screening of functional regulatory elements.
    We are using high-throughput CRISPR/Cas9-mediated genetic screening to interrogate the biological significance of a large number of non-coding regulatory sequences in the mammalian genome in both embryonic stem cells and iPSC-derived neural cell types.
  2. Charting the regulatory landscape of human brain development and function.
    We are utilizing integrative, unbiased, and high-throughput genomic and genetic tools (ATAC-seq, RNA-seq, ChIP-seq, 4C-seq, Hi-C, and CRISPR) to identify and functionally characterize cis-regulatory elements in human brain cells.
  3. Investigating the functions of non-coding genetic variation associated with neurological diseases.
    Putative regulatory regions harbor a disproportionately large number of sequence variants associated with human traits and diseases, leading to the notion that genetic lesions in the cis-regulatory elements contribute substantially to common human diseases. We are using functional genomics tools to investigate how non-coding variants associated with complex neurological disorders (e.g., autism spectrum disorders (ASD), Alzheimer diseases (AD), and Parkinson disease (PD)) contribute to disease.
Research Summary: 
Functional genomics, gene regulation, 3D chromatin architecture, and human diseases

Websites

Publications: 

SOX2 regulates acinar cell development in the salivary gland.

eLife

Emmerson E, May AJ, Nathan S, Cruz-Pacheco N, Lizama CO, Maliskova L, Zovein AC, Shen Y, Muench MO, Knox SM

A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells.

Nature methods

Diao Y, Fang R, Li B, Meng Z, Yu J, Qiu Y, Lin KC, Huang H, Liu T, Marina RJ, Jung I, Shen Y, Guan KL, Ren B

Improved regulatory element prediction based on tissue-specific local epigenomic signatures.

Proceedings of the National Academy of Sciences of the United States of America

He Y, Gorkin DU, Dickel DE, Nery JR, Castanon RG, Lee AY, Shen Y, Visel A, Pennacchio LA, Ren B, Ecker JR

A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening.

Genome research

Diao Y, Li B, Meng Z, Jung I, Lee AY, Dixon J, Maliskova L, Guan KL, Shen Y, Ren B

Chromatin architecture reorganization during stem cell differentiation.

Nature

Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE, Lee AY, Ye Z, Kim A, Rajagopal N, Xie W, Diao Y, Liang J, Zhao H, Lobanenkov VV, Ecker JR, Thomson JA, Ren B

A comparative encyclopedia of DNA elements in the mouse genome.

Nature

Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T, Sandstrom R, Ma Z, Davis C, Pope BD, Shen Y, Pervouchine DD, Djebali S, Thurman RE, Kaul R, Rynes E, Kirilusha A, Marinov GK, Williams BA, Trout D, Amrhein H, Fisher-Aylor K, Antoshechkin I, DeSalvo G, See LH, Fastuca M, Drenkow J, Zaleski C, Dobin A, Prieto P, Lagarde J, Bussotti G, Tanzer A, Denas O, Li K, Bender MA, Zhang M, Byron R, Groudine MT, McCleary D, Pham L, Ye Z, Kuan S, Edsall L, Wu YC, Rasmussen MD, Bansal MS, Kellis M, Keller CA, Morrissey CS, Mishra T, Jain D, Dogan N, Harris RS, Cayting P, Kawli T, Boyle AP, Euskirchen G, Kundaje A, Lin S, Lin Y, Jansen C, Malladi VS, Cline MS, Erickson DT, Kirkup VM, Learned K, Sloan CA, Rosenbloom KR, Lacerda de Sousa B, Beal K, Pignatelli M, Flicek P, Lian J, Kahveci T, Lee D, Kent WJ, Ramalho Santos M, Herrero J, Notredame C, Johnson A, Vong S, Lee K, Bates D, Neri F, Diegel M, Canfield T, Sabo PJ, Wilken MS, Reh TA, Giste E, Shafer A, Kutyavin T, Haugen E, Dunn D, Reynolds AP, Neph S, Humbert R, Hansen RS, De Bruijn M, Selleri L, Rudensky A, Josefowicz S, Samstein R, Eichler EE, Orkin SH, Levasseur D, Papayannopoulou T, Chang KH, Skoultchi A, Gosh S, Disteche C, Treuting P, Wang Y, Weiss MJ, Blobel GA, Cao X, Zhong S, Wang T, Good PJ, Lowdon RF, Adams LB, Zhou XQ, Pazin MJ, Feingold EA, Wold B, Taylor J, Mortazavi A, Weissman SM, Stamatoyannopoulos JA, Snyder MP, Guigo R, Gingeras TR, Gilbert DM, Hardison RC, Beer MA, Ren B

A panel of CpG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.

Stem cell reports

Huang K, Shen Y, Xue Z, Bibikova M, April C, Liu Z, Cheng L, Nagy A, Pellegrini M, Fan JB, Fan G

Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues.

Nature genetics

Hon GC, Rajagopal N, Shen Y, McCleary DF, Yue F, Dang MD, Ren B

A map of the cis-regulatory sequences in the mouse genome.

Nature

Shen Y, Yue F, McCleary DF, Ye Z, Edsall L, Kuan S, Wagner U, Dixon J, Lee L, Lobanenkov VV, Ren B

Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome.

Cell

Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A, Li X, Dai Q, Shen Y, Park B, Min JH, Jin P, Ren B, He C

Topological domains in mammalian genomes identified by analysis of chromatin interactions.

Nature

Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B

Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.

PLoS genetics

Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF

Functional modules distinguish human induced pluripotent stem cells from embryonic stem cells.

Stem cells and development

Wang A, Huang K, Shen Y, Xue Z, Cai C, Horvath S, Fan G

Genome-wide DNA methylation profiling: the mDIP-chip technology.

Methods in molecular biology (Clifton, N.J.)

Shen Y, Fouse SD, Fan G

X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.

Proceedings of the National Academy of Sciences of the United States of America

Shen Y, Matsuno Y, Fouse SD, Rao N, Root S, Xu R, Pellegrini M, Riggs AD, Fan G

Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation.

Cell stem cell

Fouse SD, Shen Y, Pellegrini M, Cole S, Meissner A, Van Neste L, Jaenisch R, Fan G

DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling.

Development (Cambridge, England)

Fan G, Martinowich K, Chin MH, He F, Fouse SD, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, ten Hoeve J, Shuai K, Sun YE