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.

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.
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.
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

Mentorship Development:

5/26/20 Effective Strategies for IDPs for Partial Resumption of Lab Research
9/11/20 Mentoring Across Differences
5/25/21 Sharpening your Mentoring Skills (SyMS)

Websites

Publications:

The PRC2.1 Subcomplex Opposes G1 Progression through Regulation of CCND1 and CCND2.

bioRxiv : the preprint server for biology

Longhurst AD, Wang K, Suresh HG, Ketavarapu M, Ward HN, Jones IR, Narayan V, Hundley FV, Hassan AZ, Boone C, Myers CL, Shen Y, Ramani V, Andrews BJ, Toczyski DP

Phase separation of YAP-MAML2 differentially regulates the transcriptome.

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

Chung CI, Yang J, Yang X, Liu H, Ma Z, Szulzewsky F, Holland EC, Shen Y, Shu X

High-throughput PRIME-editing screens identify functional DNA variants in the human genome.

Molecular cell

Ren X, Yang H, Nierenberg JL, Sun Y, Chen J, Beaman C, Pham T, Nobuhara M, Takagi MA, Narayan V, Li Y, Ziv E, Shen Y

Functional characterization of Alzheimer's disease genetic variants in microglia.

Nature genetics

Yang X, Wen J, Yang H, Jones IR, Zhu X, Liu W, Li B, Clelland CD, Luo W, Wong MY, Ren X, Cui X, Song M, Liu H, Chen C, Eng N, Ravichandran M, Sun Y, Lee D, Van Buren E, Jiang MZ, Chan CSY, Ye CJ, Perera RM, Gan L, Li Y, Shen Y

Efficient bi-allelic tagging in human induced pluripotent stem cells using CRISPR.

STAR protocols

Ren X, Takagi MA, Shen Y

High-throughput CRISPRi and CRISPRa technologies in 3D genome regulation for neuropsychiatric diseases.

Human molecular genetics

Jones IR, Ren X, Shen Y

Genetically encoded chemical crosslinking of RNA in vivo.

Nature chemistry

Sun W, Wang N, Liu H, Yu B, Jin L, Ren X, Shen Y, Wang L

Dual genome-wide coding and lncRNA screens in neural induction of induced pluripotent stem cells.

Cell genomics

Wu D, Poddar A, Ninou E, Hwang E, Cole MA, Liu SJ, Horlbeck MA, Chen J, Replogle JM, Carosso GA, Eng NWL, Chang J, Shen Y, Weissman JS, Lim DA

Coordinated transcriptional and catabolic programs support iron dependent adaptation to RAS-MAPK pathway inhibition in pancreatic cancer.

Cancer discovery

Ravichandran M, Hu J, Cai C, Ward NP, Venida A, Foakes C, Kuljanin M, Yang A, Hennessey CJ, Yang Y, Desousa BR, Rademaker G, Staes AAL, Cakir Z, Jain IH, Aguirre AJ, Mancias JD, Shen Y, DeNicola GM, Perera RM

Transcriptional network orchestrating regional patterning of cortical progenitors.

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

Ypsilanti AR, Pattabiraman K, Catta-Preta R, Golonzhka O, Lindtner S, Tang K, Jones IR, Abnousi A, Juric I, Hu M, Shen Y, Dickel DE, Visel A, Pennachio LA, Hawrylycz M, Thompson CL, Zeng H, Barozzi I, Nord AS, Rubenstein JL

An atlas of gene regulatory elements in adult mouse cerebrum.

Nature

Li YE, Preissl S, Hou X, Zhang Z, Zhang K, Qiu Y, Poirion OB, Li B, Chiou J, Liu H, Pinto-Duarte A, Kubo N, Yang X, Fang R, Wang X, Han JY, Lucero J, Yan Y, Miller M, Kuan S, Gorkin D, Gaulton KJ, Shen Y, Nunn M, Mukamel EA, Behrens MM, Ecker JR, Ren B

Parallel characterization of cis-regulatory elements for multiple genes using CRISPRpath.

Science advances

Ren X, Wang M, Li B, Jamieson K, Zheng L, Jones IR, Li B, Takagi MA, Lee J, Maliskova L, Tam TW, Yu M, Hu R, Lee L, Abnousi A, Li G, Li Y, Hu M, Ren B, Wang W, Shen Y

Deletion of CTCF sites in the SHH locus alters enhancer-promoter interactions and leads to acheiropodia.

Nature communications

Ushiki A, Zhang Y, Xiong C, Zhao J, Georgakopoulos-Soares I, Kane L, Jamieson K, Bamshad MJ, Nickerson DA, University of Washington Center for Mendelian Genomics , Shen Y, Lettice LA, Silveira-Lucas EL, Petit F, Ahituv N

The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex.

Molecular brain

Wang X, Jiang W, Luo S, Yang X, Wang C, Wang B, Dang Y, Shen Y, Ma DK

Cell-type-specific 3D epigenomes in the developing human cortex.

Nature

Song M, Pebworth MP, Yang X, Abnousi A, Fan C, Wen J, Rosen JD, Choudhary MNK, Cui X, Jones IR, Bergenholtz S, Eze UC, Juric I, Li B, Maliskova L, Lee J, Liu W, Pollen AA, Li Y, Wang T, Hu M, Kriegstein AR, Shen Y

An atlas of dynamic chromatin landscapes in mouse fetal development.

Nature

Gorkin DU, Barozzi I, Zhao Y, Zhang Y, Huang H, Lee AY, Li B, Chiou J, Wildberg A, Ding B, Zhang B, Wang M, Strattan JS, Davidson JM, Qiu Y, Afzal V, Akiyama JA, Plajzer-Frick I, Novak CS, Kato M, Garvin TH, Pham QT, Harrington AN, Mannion BJ, Lee EA, Fukuda-Yuzawa Y, He Y, Preissl S, Chee S, Han JY, Williams BA, Trout D, Amrhein H, Yang H, Cherry JM, Wang W, Gaulton K, Ecker JR, Shen Y, Dickel DE, Visel A, Pennacchio LA, Ren B

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Nature

SMART-Q: An Integrative Pipeline Quantifying Cell Type-Specific RNA Transcription.

PloS one

Yang X, Bergenholtz S, Maliskova L, Pebworth MP, Kriegstein AR, Li Y, Shen Y

SAME-clustering: Single-cell Aggregated Clustering via Mixture Model Ensemble.

Nucleic acids research

Huh R, Yang Y, Jiang Y, Shen Y, Li Y

Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes.

Nature genetics

Song M, Yang X, Ren X, Maliskova L, Li B, Jones IR, Wang C, Jacob F, Wu K, Traglia M, Tam TW, Jamieson K, Lu SY, Ming GL, Li Y, Yao J, Weiss LA, Dixon JR, Judge LM, Conklin BR, Song H, Gan L, Shen Y

Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity.

eLife

Alexander JM, Guan J, Li B, Maliskova L, Song M, Shen Y, Huang B, Lomvardas S, Weiner OD

Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain.

PLoS biology

Zhan L, Krabbe G, Du F, Jones I, Reichert MC, Telpoukhovskaia M, Kodama L, Wang C, Cho SH, Sayed F, Li Y, Le D, Zhou Y, Shen Y, West B, Gan L

Gene regulation in the 3D genome.

Human molecular genetics

Li Y, Hu M, Shen Y

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

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

Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells.

Human molecular genetics

Shen Y, Chow J, Wang Z, 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

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Yin Shen, PhD

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