Search

Your search keyword '"Cheng, Yuyan"' showing total 136 results
Start Over Author "Cheng, Yuyan"
136 results on '"Cheng, Yuyan"'

1. Single-cell genomics and regulatory networks for 388 human brains.

Author

Emani, Prashant, Liu, Jason, Clarke, Declan, Jensen, Matthew, Warrell, Jonathan, Gupta, Chirag, Meng, Ran, Lee, Che Yu, Xu, Siwei, Dursun, Cagatay, Lou, Shaoke, Chen, Yuhang, Chu, Zhiyuan, Galeev, Timur, Hwang, Ahyeon, Li, Yunyang, Ni, Pengyu, Zhou, Xiao, Bakken, Trygve, Bendl, Jaroslav, Bicks, Lucy, Chatterjee, Tanima, Cheng, Lijun, Cheng, Yuyan, Dai, Yi, Duan, Ziheng, Flaherty, Mary, Fullard, John, Gancz, Michael, Garrido-Martín, Diego, Gaynor-Gillett, Sophia, Grundman, Jennifer, Hawken, Natalie, Henry, Ella, Hoffman, Gabriel, Huang, Ao, Jiang, Yunzhe, Jin, Ting, Jorstad, Nikolas, Kawaguchi, Riki, Khullar, Saniya, Liu, Jianyin, Liu, Junhao, Liu, Shuang, Ma, Shaojie, Margolis, Michael, Mazariegos, Samantha, Moore, Jill, Moran, Jennifer, Nguyen, Eric, Phalke, Nishigandha, Pjanic, Milos, Pratt, Henry, Quintero, Diana, Rajagopalan, Ananya, Riesenmy, Tiernon, Shedd, Nicole, Shi, Manman, Spector, Megan, Terwilliger, Rosemarie, Travaglini, Kyle, Wamsley, Brie, Wang, Gaoyuan, Xia, Yan, Xiao, Shaohua, Yang, Andrew, Zheng, Suchen, Gandal, Michael, Lee, Donghoon, Lein, Ed, Roussos, Panos, Sestan, Nenad, Weng, Zhiping, White, Kevin, Won, Hyejung, Girgenti, Matthew, Zhang, Jing, Wang, Daifeng, Geschwind, Daniel, and Gerstein, Mark

Subjects
Humans, Aging, Brain, Cell Communication, Chromatin, Gene Regulatory Networks, Genomics, Mental Disorders, Prefrontal Cortex, Quantitative Trait Loci, Single-Cell Analysis
Abstract

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Published
2024

2. Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain

Author

Wen, Cindy, Margolis, Michael, Dai, Rujia, Zhang, Pan, Przytycki, Pawel F, Vo, Daniel D, Bhattacharya, Arjun, Matoba, Nana, Tang, Miao, Jiao, Chuan, Kim, Minsoo, Tsai, Ellen, Hoh, Celine, Aygün, Nil, Walker, Rebecca L, Chatzinakos, Christos, Clarke, Declan, Pratt, Henry, Peters, Mette A, Gerstein, Mark, Daskalakis, Nikolaos P, Weng, Zhiping, Jaffe, Andrew E, Kleinman, Joel E, Hyde, Thomas M, Weinberger, Daniel R, Bray, Nicholas J, Sestan, Nenad, Geschwind, Daniel H, Roeder, Kathryn, Gusev, Alexander, Pasaniuc, Bogdan, Stein, Jason L, Love, Michael I, Pollard, Katherine S, Liu, Chunyu, Gandal, Michael J, Akbarian, Schahram, Abyzov, Alexej, Ahituv, Nadav, Arasappan, Dhivya, Almagro Armenteros, Jose Juan, Beliveau, Brian J, Bendl, Jaroslav, Berretta, Sabina, Bharadwaj, Rahul A, Bicks, Lucy, Brennand, Kristen, Capauto, Davide, Champagne, Frances A, Chatterjee, Tanima, Chatzinakos, Chris, Chen, Yuhang, Chen, H Isaac, Cheng, Yuyan, Cheng, Lijun, Chess, Andrew, Chien, Jo-fan, Chu, Zhiyuan, Clement, Ashley, Collado-Torres, Leonardo, Cooper, Gregory M, Crawford, Gregory E, Davila-Velderrain, Jose, Deep-Soboslay, Amy, Deng, Chengyu, DiPietro, Christopher P, Dracheva, Stella, Drusinsky, Shiron, Duan, Ziheng, Duong, Duc, Dursun, Cagatay, Eagles, Nicholas J, Edelstein, Jonathan, Emani, Prashant S, Fullard, John F, Galani, Kiki, Galeev, Timur, Gaynor, Sophia, Girdhar, Kiran, Goes, Fernando S, Greenleaf, William, Grundman, Jennifer, Guo, Hanmin, Guo, Qiuyu, Gupta, Chirag, Hadas, Yoav, Hallmayer, Joachim, Han, Xikun, Haroutunian, Vahram, Hawken, Natalie, He, Chuan, Henry, Ella, Hicks, Stephanie C, Ho, Marcus, Ho, Li-Lun, Hoffman, Gabriel E, Huang, Yiling, Huuki-Myers, Louise A, and Hwang, Ahyeon

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biological Psychology, Psychology, Mental Illness, Mental Health, Human Genome, Neurosciences, Brain Disorders, Mental health, Humans, Alternative Splicing, Atlases as Topic, Autism Spectrum Disorder, Brain, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genome-Wide Association Study, Protein Isoforms, Quantitative Trait Loci, Schizophrenia, Transcriptome, Mental Disorders, PsychENCODE Consortium†, PsychENCODE Consortium, General Science & Technology
Abstract

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.

Published
2024

3. Massively parallel characterization of regulatory elements in the developing human cortex

Author

Deng, Chengyu, Whalen, Sean, Steyert, Marilyn, Ziffra, Ryan, Przytycki, Pawel F, Inoue, Fumitaka, Pereira, Daniela A, Capauto, Davide, Norton, Scott, Vaccarino, Flora M, Pollen, Alex A, Nowakowski, Tomasz J, Ahituv, Nadav, Pollard, Katherine S, Akbarian, Schahram, Abyzov, Alexej, Arasappan, Dhivya, Almagro Armenteros, Jose Juan, Beliveau, Brian J, Bendl, Jaroslav, Berretta, Sabina, Bharadwaj, Rahul A, Bhattacharya, Arjun, Bicks, Lucy, Brennand, Kristen, Champagne, Frances A, Chatterjee, Tanima, Chatzinakos, Chris, Chen, Yuhang, Chen, H Isaac, Cheng, Yuyan, Cheng, Lijun, Chess, Andrew, Chien, Jo-fan, Chu, Zhiyuan, Clarke, Declan, Clement, Ashley, Collado-Torres, Leonardo, Cooper, Gregory M, Crawford, Gregory E, Dai, Rujia, Daskalakis, Nikolaos P, Davila-Velderrain, Jose, Deep-Soboslay, Amy, DiPietro, Christopher P, Dracheva, Stella, Drusinsky, Shiron, Duan, Ziheng, Duong, Duc, Dursun, Cagatay, Eagles, Nicholas J, Edelstein, Jonathan, Emani, Prashant S, Fullard, John F, Galani, Kiki, Galeev, Timur, Gandal, Michael J, Gaynor, Sophia, Gerstein, Mark, Geschwind, Daniel H, Girdhar, Kiran, Goes, Fernando S, Greenleaf, William, Grundman, Jennifer, Guo, Hanmin, Guo, Qiuyu, Gupta, Chirag, Hadas, Yoav, Hallmayer, Joachim, Han, Xikun, Haroutunian, Vahram, Hawken, Natalie, He, Chuan, Henry, Ella, Hicks, Stephanie C, Ho, Marcus, Ho, Li-Lun, Hoffman, Gabriel E, Huang, Yiling, Huuki-Myers, Louise A, Hwang, Ahyeon, Hyde, Thomas M, Iatrou, Artemis, Jajoo, Aarti, Jensen, Matthew, Jiang, Lihua, Jin, Peng, Jin, Ting, Jops, Connor, Jourdon, Alexandre, Kawaguchi, Riki, Kellis, Manolis, Khullar, Saniya, Kleinman, Joel E, Kleopoulos, Steven P, and Kozlenkov, Alex

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Stem Cell Research - Embryonic - Human, Stem Cell Research, Human Genome, Genetics, Neurosciences, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Neurological, Humans, Cerebral Cortex, Chromatin, Deep Learning, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Neurogenesis, Neurons, Organoids, Regulatory Sequences, Nucleic Acid, Promoter Regions, Genetic, Regulatory Elements, Transcriptional, PsychENCODE Consortium‡, PsychENCODE Consortium, General Science & Technology
Abstract

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Published
2024

5. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Author

Tian, Feng, Cheng, Yuyan, Zhou, Songlin, Wang, Qianbin, Monavarfeshani, Aboozar, Gao, Kun, Jiang, Weiqian, Kawaguchi, Riki, Wang, Qing, Tang, Mingjun, Donahue, Ryan, Meng, Huyan, Zhang, Yu, Jacobi, Anne, Yan, Wenjun, Yin, Jiani, Cai, Xinyi, Yang, Zhiyun, Hegarty, Shane, Stanicka, Joanna, Dmitriev, Phillip, Taub, Daniel, Zhu, Junjie, Woolf, Clifford, Sanes, Joshua, He, Zhigang, and Geschwind, Daniel

Subjects
ATF3, ATF4, C/EBPg, CHOP, axon regeneration and neuronal degeneration, optic nerve, retinal ganglion cell, Animals, Axons, Mice, Mice, Inbred C57BL, Nerve Regeneration, Optic Nerve Injuries, Retinal Ganglion Cells
Abstract

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

Published
2022

6. Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics

Author

Rexach, Jessica E., Cheng, Yuyan, Chen, Lawrence, Polioudakis, Damon, Lin, Li-Chun, Mitri, Vivianne, Elkins, Andrew, Han, Xia, Yamakawa, Mai, Yin, Anna, Calini, Daniela, Kawaguchi, Riki, Ou, Jing, Huang, Jerry, Williams, Christopher, Robinson, John, Gaus, Stephanie E., Spina, Salvatore, Lee, Edward B., Grinberg, Lea T., Vinters, Harry, Trojanowski, John Q., Seeley, William W., Malhotra, Dheeraj, and Geschwind, Daniel H.

Published
2024
Full Text
View/download PDF

7. Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice

Author

Cheng, Yuyan, Yin, Yuqin, Zhang, Alice, Bernstein, Alexander M, Kawaguchi, Riki, Gao, Kun, Potter, Kyra, Gilbert, Hui-Ya, Ao, Yan, Ou, Jing, Fricano-Kugler, Catherine J, Goldberg, Jeffrey L, He, Zhigang, Woolf, Clifford J, Sofroniew, Michael V, Benowitz, Larry I, and Geschwind, Daniel H

Subjects
Biotechnology, Genetics, Neurosciences, Neurodegenerative, Regenerative Medicine, Spinal Cord Injury, Traumatic Head and Spine Injury, Physical Injury - Accidents and Adverse Effects, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Animals, Axons, Mice, Nerve Regeneration, Repressor Proteins, Retinal Ganglion Cells, Spinal Cord Injuries, Transcription Factors
Abstract

The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.

Published
2022

10. Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders

Author

Xia, Yan, primary, Xia, Cuihua, additional, Jiang, Yi, additional, Chen, Yu, additional, Zhou, Jiaqi, additional, Dai, Rujia, additional, Han, Cong, additional, Mao, Zhongzheng, additional, Consortium, PsychENCODE, additional, Liu, Chunyu, additional, Chen, Chao, additional, Akbarian, Schahram, additional, Abyzov, Alexej, additional, Ahituv, Nadav, additional, Arasappan, Dhivya, additional, Almagro Armenteros, Jose Juan, additional, Beliveau, Brian J., additional, Bendl, Jaroslav, additional, Berretta, Sabina, additional, Bharadwaj, Rahul A., additional, Bhattacharya, Arjun, additional, Bicks, Lucy, additional, Brennand, Kristen, additional, Capauto, Davide, additional, Champagne, Frances A., additional, Chatterjee, Tanima, additional, Chatzinakos, Chris, additional, Chen, Yuhang, additional, Chen, H. Isaac, additional, Cheng, Yuyan, additional, Cheng, Lijun, additional, Chess, Andrew, additional, Chien, Jo-fan, additional, Chu, Zhiyuan, additional, Clarke, Declan, additional, Clement, Ashley, additional, Collado-Torres, Leonardo, additional, Cooper, Gregory M., additional, Crawford, Gregory E., additional, Daskalakis, Nikolaos P., additional, Davila-Velderrain, Jose, additional, Deep-Soboslay, Amy, additional, Deng, Chengyu, additional, DiPietro, Christopher P., additional, Dracheva, Stella, additional, Drusinsky, Shiron, additional, Duan, Ziheng, additional, Duong, Duc, additional, Dursun, Cagatay, additional, Eagles, Nicholas J., additional, Edelstein, Jonathan, additional, Emani, Prashant S., additional, Fullard, John F., additional, Galani, Kiki, additional, Galeev, Timur, additional, Gandal, Michael J., additional, Gaynor, Sophia, additional, Gerstein, Mark, additional, Geschwind, Daniel H., additional, Girdhar, Kiran, additional, Goes, Fernando S., additional, Greenleaf, William, additional, Grundman, Jennifer, additional, Guo, Hanmin, additional, Guo, Qiuyu, additional, Gupta, Chirag, additional, Hadas, Yoav, additional, Hallmayer, Joachim, additional, Han, Xikun, additional, Haroutunian, Vahram, additional, Hawken, Natalie, additional, He, Chuan, additional, Henry, Ella, additional, Hicks, Stephanie C., additional, Ho, Marcus, additional, Ho, Li-Lun, additional, Hoffman, Gabriel E., additional, Huang, Yiling, additional, Huuki-Myers, Louise A., additional, Hwang, Ahyeon, additional, Hyde, Thomas M., additional, Iatrou, Artemis, additional, Inoue, Fumitaka, additional, Jajoo, Aarti, additional, Jensen, Matthew, additional, Jiang, Lihua, additional, Jin, Peng, additional, Jin, Ting, additional, Jops, Connor, additional, Jourdon, Alexandre, additional, Kawaguchi, Riki, additional, Kellis, Manolis, additional, Khullar, Saniya, additional, Kleinman, Joel E., additional, Kleopoulos, Steven P., additional, Kozlenkov, Alex, additional, Kriegstein, Arnold, additional, Kundaje, Anshul, additional, Kundu, Soumya, additional, Lee, Cheyu, additional, Lee, Donghoon, additional, Li, Junhao, additional, Li, Mingfeng, additional, Lin, Xiao, additional, Liu, Shuang, additional, Liu, Jason, additional, Liu, Jianyin, additional, Lou, Shaoke, additional, Loupe, Jacob M., additional, Lu, Dan, additional, Ma, Shaojie, additional, Ma, Liang, additional, Margolis, Michael, additional, Mariani, Jessica, additional, Martinowich, Keri, additional, Maynard, Kristen R., additional, Mazariegos, Samantha, additional, Meng, Ran, additional, Myers, Richard M., additional, Micallef, Courtney, additional, Mikhailova, Tatiana, additional, Ming, Guo-li, additional, Mohammadi, Shahin, additional, Monte, Emma, additional, Montgomery, Kelsey S., additional, Moore, Jill E., additional, Moran, Jennifer R., additional, Mukamel, Eran A., additional, Nairn, Angus C., additional, Nemeroff, Charles B., additional, Ni, Pengyu, additional, Norton, Scott, additional, Nowakowski, Tomasz, additional, Omberg, Larsson, additional, Page, Stephanie C., additional, Park, Saejeong, additional, Patowary, Ashok, additional, Pattni, Reenal, additional, Pertea, Geo, additional, Peters, Mette A., additional, Phalke, Nishigandha, additional, Pinto, Dalila, additional, Pjanic, Milos, additional, Pochareddy, Sirisha, additional, Pollard, Katherine S., additional, Pollen, Alex, additional, Pratt, Henry, additional, Przytycki, Pawel F., additional, Purmann, Carolin, additional, Qin, Zhaohui S., additional, Qu, Ping-Ping, additional, Quintero, Diana, additional, Raj, Towfique, additional, Rajagopalan, Ananya S., additional, Reach, Sarah, additional, Reimonn, Thomas, additional, Ressler, Kerry J., additional, Ross, Deanna, additional, Roussos, Panos, additional, Rozowsky, Joel, additional, Ruth, Misir, additional, Ruzicka, W. Brad, additional, Sanders, Stephan J., additional, Schneider, Juliane M., additional, Scuderi, Soraya, additional, Sebra, Robert, additional, Sestan, Nenad, additional, Seyfried, Nicholas, additional, Shao, Zhiping, additional, Shedd, Nicole, additional, Shieh, Annie W., additional, Shin, Joo Heon, additional, Skarica, Mario, additional, Snijders, Clara, additional, Song, Hongjun, additional, State, Matthew W., additional, Stein, Jason, additional, Steyert, Marilyn, additional, Subburaju, Sivan, additional, Sudhof, Thomas, additional, Snyder, Michael, additional, Tao, Ran, additional, Therrien, Karen, additional, Tsai, Li-Huei, additional, Urban, Alexander E., additional, Vaccarino, Flora M., additional, van Bake, Harm, additional, Vo, Daniel, additional, Voloudakis, Georgios, additional, Wamsley, Brie, additional, Wang, Tao, additional, Wang, Sidney H., additional, Wang, Daifeng, additional, Wang, Yifan, additional, Warrell, Jonathan, additional, Wei, Yu, additional, Weimer, Annika K., additional, Weinberger, Daniel R., additional, Wen, Cindy, additional, Weng, Zhiping, additional, Whalen, Sean, additional, White, Kevin P., additional, Willsey, A. Jeremy, additional, Won, Hyejung, additional, Wong, Wing, additional, Wu, Hao, additional, Wu, Feinan, additional, Wuchty, Stefan, additional, Wylie, Dennis, additional, Xu, Siwei, additional, Yap, Chloe X., additional, Zeng, Biao, additional, Zhang, Pan, additional, Zhang, Chunling, additional, Zhang, Bin, additional, Zhang, Jing, additional, Zhang, Yanqiong, additional, Zhou, Xiao, additional, Ziffra, Ryan, additional, Zeier, Zane R., additional, and Zintel, Trisha M., additional

Published
2024
Full Text
View/download PDF

11. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Author

Tian, Feng, Cheng, Yuyan, Zhou, Songlin, Wang, Qianbin, Monavarfeshani, Aboozar, Gao, Kun, Jiang, Weiqian, Kawaguchi, Riki, Wang, Qing, Tang, Mingjun, Donahue, Ryan, Meng, Huyan, Zhang, Yu, Jacobi, Anne, Yan, Wenjun, Yin, Jiani, Cai, Xinyi, Yang, Zhiyun, Hegarty, Shane, and Stanicka, Joanna

Subjects
*RETINAL ganglion cells, *GENETIC transcription, *MELANOPSIN, *NEURODEGENERATION
Published
2024
Full Text
View/download PDF

13. Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cell genomics

Author

Rexach, Jessica E, primary, Cheng, Yuyan, additional, Chen, Lawrence, additional, Polioudakis, Damon, additional, Lin, Li-Chun, additional, Mitri, Vivanne, additional, Elkins, Andrew, additional, Yin, Anna, additional, Calini, Daniela, additional, Kawaguchi, Riki, additional, Ou, Jing, additional, Huang, Jerry, additional, Williams, Christopher, additional, Robinson, John, additional, Gaus, Stephanie, additional, Spina, Salvatore, additional, Lee, Edward, additional, Grinberg, Lea, additional, Vinters, Harry, additional, Trojanowski, John, additional, Seeley, William, additional, Molhatra, Dheeraj, additional, and Geschwind, Daniel, additional

Published
2023
Full Text
View/download PDF

18. Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program

Author

Cheah, Menghon, Cheng, Yuyan, Petrova, Veselina, Cimpean, Anda, Jendelova, Pavla, Swarup, Vivek, Woolf, Clifford J, Geschwind, Daniel H, Fawcett, James W, Swarup, Vivek [0000-0003-3762-2746], Woolf, Clifford J [0000-0002-6636-3897], Fawcett, James W [0000-0002-7990-4568], and Apollo - University of Cambridge Repository

Subjects
Male, autophagy, Integrins, Sensory Receptor Cells, integrin, axon regeneration, spinal cord, sensory, Axons, Rats, Nerve Regeneration, Rats, Sprague-Dawley, nervous system, Ganglia, Spinal, Humans, Animals, signaling, Spinal Cord Injuries
Abstract

The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.

Published
2023

20. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells

Author

Tian, Feng, primary, Cheng, Yuyan, additional, Zhou, Songlin, additional, Wang, Qianbin, additional, Monavarfeshani, Aboozar, additional, Gao, Kun, additional, Jiang, Weiqian, additional, Kawaguchi, Riki, additional, Wang, Qing, additional, Tang, Mingjun, additional, Donahue, Ryan, additional, Meng, Huyan, additional, Zhang, Yu, additional, Jacobi, Anne, additional, Yan, Wenjun, additional, Yin, Jiani, additional, Cai, Xinyi, additional, Yang, Zhiyun, additional, Hegarty, Shane, additional, Stanicka, Joanna, additional, Dmitriev, Phillip, additional, Taub, Daniel, additional, Zhu, Junjie, additional, Woolf, Clifford J., additional, Sanes, Joshua R., additional, Geschwind, Daniel H., additional, and He, Zhigang, additional

Published
2023
Full Text
View/download PDF

22. Molecular cascades and cell-type specific signatures in ASD revealed by single cell genomics

Author

Wamsley, Brie, Bicks, Lucy, Cheng, Yuyan, Kawaguchi, Riki, Quintero, Diana, Grundman, Jennifer, Liu, Jianyin, Xiao, Shaohua, Hawken, Natalie, Margolis, Michael, Mazariegos, Samantha, and Geschwind, Daniel H

Subjects
Article
Abstract

Understanding how genetic variation exerts its effects on the human brain in health and disease has been greatly informed by functional genomic characterization. Studies over the last decade have demonstrated robust evidence of convergent transcriptional and epigenetic profiles in post-mortem cerebral cortex from individuals with Autism Spectrum Disorder (ASD). Here, we perform deep single nuclear (sn) RNAseq to elucidate changes in cell composition, cellular transcriptomes and putative candidate drivers associated with ASD, which we corroborate using snATAC-seq and spatial profiling. We find changes in cell state composition representing transitions from homeostatic to reactive profiles in microglia and astrocytes, a pattern extending to oligodendrocytes and blood brain barrier cells. We identify profound changes in differential expression involving thousands of genes across neuronal and glial subtypes, of which a substantial portion can be accounted for by specific transcription factor networks that are significantly enriched in common and rare genetic risk for ASD. These data, which are available as part of the PsychENCODE consortium, provide robust causal anchors and resultant molecular phenotypes for understanding ASD changes in human brain.

Published
2023

23. Correction: Author Correction: Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Author

Zuo, Xianbo, Sun, Liangdan, Yin, Xianyong, Gao, Jinping, Sheng, Yujun, Xu, Jinhua, Zhang, Jianzhong, He, Chundi, Qiu, Ying, Wen, Guangdong, Tian, Hongqing, Zheng, Xiaodong, Liu, Shengxiu, Wang, Wenjun, Li, Weiran, Cheng, Yuyan, Liu, Longdan, Chang, Yan, Wang, Zaixing, Li, Zenggang, Li, Longnian, Wu, Jianping, Fang, Ling, Shen, Changbing, Zhou, Fusheng, Liang, Bo, Chen, Gang, Li, Hui, Cui, Yong, Xu, Aie, Yang, Xueqin, Hao, Fei, Xu, Limin, Fan, Xing, Li, Yuzhen, Wu, Rina, Wang, Xiuli, Liu, Xiaoming, Zheng, Min, Song, Shunpeng, Ji, Bihua, Fang, Hong, Yu, Jianbin, Sun, Yongxin, Hui, Yan, Zhang, Furen, Yang, Rongya, Yang, Sen, and Zhang, Xuejun

Published
2018
Full Text
View/download PDF

26. An Intermittent Fasting Mimetic Drives Plasticity Via an Adaptive ER Stress-ATF4 Pathwayand Elicits Stroke Recovery and Alzheimer's Resilience

Author

Kumar, Amit, primary, Karuppagounder, Saravanan S., additional, Chen, Yingxin, additional, Corona, Carlo, additional, Kawaguchi, Riki, additional, Cheng, Yuyan, additional, Balkaya, Mustafa, additional, Sagdullaev, Botir T., additional, Wen, Zhexing, additional, Stuart, Charles, additional, Cho, Sunghee, additional, Ming, Guo-li, additional, Tuvikene, Jürgen, additional, Timmusk, Tõnis, additional, Geschwind, Daniel H., additional, and Ratan, Rajiv R., additional

Published
2022
Full Text
View/download PDF

30. Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration

Author

Cheng, Yuyan, primary, Yin, Yuqin, additional, Zhang, Alice, additional, Bernstein, Alexander M., additional, Kawaguchi, Riki, additional, Gao, Kun, additional, Potter, Kyra, additional, Gilbert, Hui-Ya, additional, Ao, Yan, additional, Ou, Jing, additional, Fricano-Kugler, Catherine J., additional, Goldberg, Jeffrey L., additional, Woolf, Clifford J., additional, Sofroniew, Michael V., additional, Benowitz, Larry I., additional, and Geschwind, Daniel H., additional

Published
2020
Full Text
View/download PDF

35. Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel

Author

Yang, Chao, primary, Wu, Juan, additional, Zhang, Xuelei, additional, Wen, Leilei, additional, Sun, Jingying, additional, Cheng, Yuyan, additional, Tang, Xianfa, additional, Liang, Bo, additional, Chen, Gang, additional, Zhou, Fusheng, additional, Cui, Yong, additional, Zhang, Anping, additional, Zhang, Xuejun, additional, Zheng, Xiaodong, additional, Yang, Sen, additional, and Sun, Liangdan, additional

Published
2018
Full Text
View/download PDF

36. Genotype combination contributes to psoriasis: An exhaustive algorithm perspective

Author

Dou, Jinfa, primary, Guo, Huimin, additional, Cheng, Fang, additional, Huang, Hequn, additional, Fu, Liying, additional, Li, Longnian, additional, Yang, Chao, additional, Ye, Lei, additional, Wen, Leilei, additional, Cheng, Yuyan, additional, Tang, Lili, additional, Zhu, Caihong, additional, Zhu, Zhengwei, additional, Wang, Wenjun, additional, Sheng, Yujun, additional, Wang, Zaixing, additional, Liu, Shengxiu, additional, Fan, Xing, additional, Zuo, Xianbo, additional, Zhou, Fusheng, additional, Sun, Liangdan, additional, Zheng, Xiaodong, additional, and Zhang, Xuejun, additional

Published
2017
Full Text
View/download PDF

37. Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development

Author

Chang, Kun-Che, primary, Hertz, Jonathan, additional, Zhang, Xiong, additional, Jin, Xiao-Lu, additional, Shaw, Peter, additional, Derosa, Brooke A., additional, Li, Janet Y., additional, Venugopalan, Praseeda, additional, Valenzuela, Daniel A., additional, Patel, Roshni D., additional, Russano, Kristina R., additional, Alshamekh, Shomoukh A., additional, Sun, Catalina, additional, Tenerelli, Kevin, additional, Li, Chenyi, additional, Velmeshev, Dmitri, additional, Cheng, Yuyan, additional, Boyce, Timothy M., additional, Dreyfuss, Alexandra, additional, Uddin, Mohammed S., additional, Muller, Kenneth J., additional, Dykxhoorn, Derek M., additional, and Goldberg, Jeffrey L., additional

Published
2017
Full Text
View/download PDF

41. Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis

Author

Zhou, Fusheng, primary, Shen, Changbing, additional, Xu, Jingkai, additional, Gao, Jing, additional, Zheng, Xiaodong, additional, Ko, Randy, additional, Dou, Jinfa, additional, Cheng, Yuyan, additional, Zhu, Caihong, additional, Xu, Shuangjun, additional, Tang, Xianfa, additional, Zuo, Xianbo, additional, Yin, Xianyong, additional, Cui, Yong, additional, Sun, Liangdan, additional, Tsoi, Lam C., additional, Hsu, Yi-Hsiang, additional, Yang, Sen, additional, and Zhang, Xuejun, additional

Published
2016
Full Text
View/download PDF

43. A rare variant in COL11A1 is strongly associated with adult height in Chinese Han population

Author

Shen, Changbing, primary, Zheng, Xiaodong, additional, Gao, Jing, additional, Zhu, Caihong, additional, Ko, Randy, additional, Tang, Xianfa, additional, Yang, Chao, additional, Dou, Jinfa, additional, Lin, Yan, additional, Cheng, Yuyan, additional, Liu, Lu, additional, Xu, Shuangjun, additional, Chen, Gang, additional, Zuo, Xianbo, additional, Yin, Xianyong, additional, Sun, Liangdan, additional, Cui, Yong, additional, Yang, Sen, additional, Zhang, Xuejun, additional, and Zhou, Fusheng, additional

Published
2016
Full Text
View/download PDF

44. Discovery of a novel genetic susceptibility locus on X chromosome for systemic lupus erythematosus

Author

Zhu, Zhengwei, primary, Liang, Zhuoyuan, additional, Liany, Herty, additional, Yang, Chao, additional, Wen, Leilei, additional, Lin, Zhiming, additional, Sheng, Yujun, additional, Lin, Yan, additional, Ye, Lei, additional, Cheng, Yuyan, additional, Chang, Yan, additional, Liu, Lu, additional, Yang, Lulu, additional, Shi, Yinjuan, additional, Shen, Changbing, additional, Zhou, Fusheng, additional, Zheng, Xiaodong, additional, Zhu, Jun, additional, Liang, Bo, additional, Ding, Yantao, additional, Zhou, Yi, additional, Yin, Xianyong, additional, Tang, Huayang, additional, Zuo, Xianbo, additional, Sun, Liangdan, additional, Bei, Jin-Xin, additional, Liu, Jianjun, additional, Yang, Sen, additional, Yang, Wanling, additional, Cui, Yong, additional, and Zhang, Xuejun, additional

Published
2015
Full Text
View/download PDF

47. Downregulated expression ofLBHmRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

Author

Chang, Yan, primary, Sheng, Yujun, additional, Cheng, Yuyan, additional, Lin, Yan, additional, Zhu, Zhengwei, additional, Wen, Leilei, additional, Yang, Chao, additional, Yang, Lulu, additional, Liu, Lu, additional, Zhou, Fusheng, additional, Zheng, Xiaodong, additional, Zhang, Shengquan, additional, Cui, Yong, additional, Yang, Sen, additional, and Zhang, Xuejun, additional

Published
2015
Full Text
View/download PDF

49. Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Author

Zuo, Xianbo, primary, Sun, Liangdan, additional, Yin, Xianyong, additional, Gao, Jinping, additional, Sheng, Yujun, additional, Xu, Jinhua, additional, Zhang, Jianzhong, additional, He, Chundi, additional, Qiu, Ying, additional, Wen, Guangdong, additional, Tian, Hongqing, additional, Zheng, Xiaodong, additional, Liu, Shengxiu, additional, Wang, Wenjun, additional, Li, Weiran, additional, Cheng, Yuyan, additional, Liu, Longdan, additional, Chang, Yan, additional, Wang, Zaixing, additional, Li, Zenggang, additional, Li, Longnian, additional, Wu, Jianping, additional, Fang, Ling, additional, Shen, Changbing, additional, Zhou, Fusheng, additional, Liang, Bo, additional, Chen, Gang, additional, Li, Hui, additional, Cui, Yong, additional, Xu, Aie, additional, Yang, Xueqin, additional, Hao, Fei, additional, Xu, Limin, additional, Fan, Xing, additional, Li, Yuzhen, additional, Wu, Rina, additional, Wang, Xiuli, additional, Liu, Xiaoming, additional, Zheng, Min, additional, Song, Shunpeng, additional, Ji, Bihua, additional, Fang, Hong, additional, Yu, Jianbin, additional, Sun, Yongxin, additional, Hui, Yan, additional, Zhang, Furen, additional, Yang, Rongya, additional, Yang, Sen, additional, and Zhang, Xuejun, additional

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results