Article
Biochemistry & Molecular Biology
Yu Han, Yuan Zhou
Summary: In this study, cell-type-specific miRNAs were identified using multiple correspondence analysis and Gini coefficients, resulting in collections of chromatin activity-specific miRNAs in 91 cell types and expression-specific miRNAs in 124 cell types. It was found that cell-type-specific miRNAs are closely associated with disease miRNAs, providing important clues for research on cancer prognosis and other aspects. Additionally, the online tool mirCellType was constructed for dissecting the cell type composition of complex samples with miRNA expression profiles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Ning Qing Liu, Michela Maresca, Teun van den Brand, Luca Braccioli, Marijne M. G. A. Schijns, Hans Teunissen, Benoit G. Bruneau, Elphege P. Nora, Elzo de Wit
Summary: WAPL generates a pool of free cohesin through cohesin turnover, which reloads it to cell-type-specific binding sites. The binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 and SOX2.
Article
Multidisciplinary Sciences
Leon van Gurp, Leon Fodoulian, Daniel Oropeza, Kenichiro Furuyama, Eva Bru-Tari, Anh Nguyet Vu, John S. Kaddis, Ivan Rodriguez, Fabrizio Thorel, Pedro L. Herrera
Summary: The authors used single-cell transcriptomics meta-analysis to construct gene sets that accurately describe the identity of various human islet cells. These gene sets have proven effective in analyzing cell identity changes and their underlying genetic mechanisms, providing reliable tools for cell therapy and diabetes treatment.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Xi Chen, Jian Zhou, Ran Zhang, Aaron K. Wong, Christopher Y. Park, Chandra L. Theesfeld, Olga G. Troyanskaya
Summary: The FENRIR framework integrates diverse epigenetic and functional genomics datasets to infer tissue-specific functional relationships between enhancers and identify disease-associated enhancers accurately. In a case study on autism, FENRIR effectively prioritized enhancers with pathogenic signals and experimentally validated their differential regulatory potential. FENRIR provides an accurate and effective approach to study tissue-specific enhancers and their role in diseases.
Article
Biochemistry & Molecular Biology
Ziyu Lu, Melissa Zhang, Jasper Lee, Andras Sziraki, Sonya Anderson, Zehao Zhang, Zihan Xu, Weirong Jiang, Shaoyu Ge, Peter T. Nelson, Wei Zhou, Junyue Cao
Summary: Progenitor cells in the aged brain play a critical role in maintaining organismal homeostasis, but their diversity and dynamics have been overlooked. A new single-cell genomic method called TrackerSci was introduced to characterize the transcriptome and chromatin landscape of proliferating progenitor cells in vivo. The study revealed diverse progenitor cell types in the brain and identified aging-associated shifts in cell-type-specific proliferation and differentiation. Conserved genetic signatures across species were also discovered in the progenitor cells of the aged human brain, along with region-specific cellular dynamics.
Article
Clinical Neurology
Fuze Zheng, Liangliang Qiu, Long Chen, Ying Zheng, Xiaodan Lin, Junjie He, Xin Lin, Qifang He, Yuhua Lin, Lin Lin, Lili Wang, Feng Lin, Kang Yang, Minting Lin, Yi Lin, Ying Fu, Ning Wang, Zhiqiang Wang
Summary: The study found that the regional methylation levels at the most distal D4Z4 repeat units were associated with disease severity and progression in FSHD1. Lower methylation levels were correlated with higher clinical scores and earlier onset of muscle weakness. CpG6 methylation levels could distinguish FSHD1 patients from healthy controls and differentiate symptomatic from asymptomatic patients.
Article
Multidisciplinary Sciences
Chang Su, Zichun Xu, Xinning Shan, Biao Cai, Hongyu Zhao, Jingfei Zhang
Summary: The advancement of scRNA-seq technology enables the direct inference of co-expressions in specific cell types, but existing methods fail to address the challenges of sequencing depth variations and measurement errors. CS-CORE is a statistical approach that accurately estimates and tests cell-type-specific co-expressions while considering these challenges. Evaluations demonstrate that CS-CORE outperforms existing methods in terms of accuracy and identification of relevant co-expressions. Applied to scRNA-seq data from Alzheimer's disease and COVID-19 patients, CS-CORE identifies reproducible and biologically relevant cell-type-specific co-expressions and differential co-expressions.
NATURE COMMUNICATIONS
(2023)
Review
Biochemical Research Methods
Maria K. Jaakkola, Laura L. Elo
Summary: This study compares the accuracy of nine different methods in estimating cell type-specific differentially expressed genes. The sensitivity to various factors present in real studies was also tested, and practical guidelines for end users were provided.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biology
Markus Muckenhuber, Isabelle Seufert, Katharina Mueller-Ott, Jan-Philipp Mallm, Lara C. Klett, Caroline Knotz, Jana Hechler, Nick Kepper, Fabian Erdel, Karsten Rippe
Summary: The antiviral response induced by type I interferon via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes across human and mouse tissues but varies between cell types. However, the links between the underlying epigenetic features and the ISG profile are not well understood.
LIFE SCIENCE ALLIANCE
(2023)
Article
Genetics & Heredity
Siqi Zhao, Clarice K. Y. Hong, Connie A. Myers, David M. Granas, Michael A. White, Joseph C. Corbo, Barak A. Cohen
Summary: Massively parallel reporter gene assays are essential for regulatory genomics but lack the ability to identify cell-type-specific regulatory elements without sequential assays. To overcome this, a single-cell massively parallel reporter assay (scMPRA) was developed to simultaneously measure the activity of libraries of cis-regulatory sequences (CRSs) across multiple cell types. The scMPRA was shown to be reproducible and capable of detecting cell-type-specific cis-regulatory activity using a library of core promoters in HEK293 and K562 cells. Furthermore, scMPRA was used to measure promoter variants in live mouse retinas, revealing that subtle genetic variations can result in cell-type-specific effects on cis-regulatory activity. The scMPRA is expected to have wide applications in studying CRSs in different cell types.
Article
Cell Biology
Yalan Yang, Runwei Yang, Bowei Kang, Sheng Qian, Xin He, Xiaochang Zhang
Summary: This study used single-cell long-read sequencing to identify a large number of cell-type-specific splicing events and uncatalogued isoforms in human neural development. Retained neuronal introns were found to be enriched in RNA splicing regulators and had shorter lengths, higher GC contents, and weaker 50 splice sites. Cell-type-specific exons in autism pro-bands were found to have significantly more de novo mutations. These findings highlight the importance of cell-type-specific splicing in autism and neuronal gene regulation.
Article
Neurosciences
Dan Liang, Angela L. Elwell, Nil Aygun, Oleh Krupa, Justin M. Wolter, Felix A. Kyere, Michael J. Lafferty, Kerry E. Cheek, Kenan P. Courtney, Marianna Yusupova, Melanie E. Garrett, Allison Ashley-Koch, Gregory E. Crawford, Michael I. Love, Luis de la Torre-ubieta, Daniel H. Geschwind, Jason L. Stein
Summary: Cell-type-specific chromatin accessibility QTL during neurogenesis allow fine mapping of causal variants, revealing regulatory mechanisms underlying noncoding loci associated with gene expression and neuropsychiatric disorders. Mutations disrupting transcriptional activators generally decrease chromatin accessibility, while mutations disrupting repressors increase chromatin accessibility.
NATURE NEUROSCIENCE
(2021)
Article
Cell & Tissue Engineering
Mariela Cortes-Lopez, Paulina Chamely, Allegra G. Hawkins, Robert F. Stanley, Ariel D. Swett, Saravanan Ganesan, Tarek H. Mouhieddine, Xiaoguang Dai, Lloyd Kluegel, Celine Chen, Kiran Batta, Nili Furer, Rahul S. Vedula, John Beaulaurier, Alexander W. Drong, Scott Hickey, Neville Dusaj, Gavriel Mullokandov, Adam M. Stasiw, Jiayu Su, Ronan Chaligne, Sissel Juul, Eoghan Harrington, David A. Knowles, Catherine J. Potenski, Daniel H. Wiseman, Amos Tanay, Liran Shlush, Robert C. Lindsley, Irene M. Ghobrial, Justin Taylor, Omar Abdel-Wahab, Federico Gaiti, Dan A. Landau
Summary: In this study, the impact of mutated splicing factors on RNA splicing during hematopoiesis was investigated using a combination of genotyping of transcriptomes, long-read single-cell transcriptomics, and proteogenomics. The study found that mutations in the core splicing factor SF3B1 led to expansion of erythroid progenitor cells, as well as stage-specific aberrant splicing during erythroid differentiation. Additionally, the study revealed specific cryptic 30 splice site usage in SF3B1-mutated cells and an erythroid bias in clonal hematopoiesis samples before overt myelodysplastic syndrome.
Article
Multidisciplinary Sciences
Warren Winick-Ng, Alexander Kukalev, Izabela Harabula, Luna Zea-Redondo, Dominik Szabo, Mandy Meijer, Leonid Serebreni, Yingnan Zhang, Simona Bianco, Andrea M. Chiariello, Ibai Irastorza-Azcarate, Christoph J. Thieme, Thomas M. Sparks, Silvia Carvalho, Luca Fiorillo, Francesco Musella, Ehsan Irani, Elena Torlai Triglia, Aleksandra A. Kolodziejczyk, Andreas Abentung, Galina Apostolova, Eleanor J. Paul, Vedran Franke, Rieke Kempfer, Altuna Akalin, Sarah A. Teichmann, Georg Dechant, Mark A. Ungless, Mario Nicodemi, Lonnie Welch, Goncalo Castelo-Branco, Ana Pombo
Summary: The 3D structure of chromatin is crucial for gene regulation and cell function. A new method called immunoGAM has been developed to map 3D chromatin topology in specific brain cell types at a genome-wide scale. The results show that highly specific chromatin conformations in brain cells are closely related to gene regulation mechanisms and specialized functions.
Article
Multidisciplinary Sciences
Aleksandr Ianevski, Anil K. Giri, Tero Aittokallio
Summary: We developed a computational platform, ScType, for automated and fast cell-type identification using scRNA-seq data and a comprehensive cell marker database. ScType provides unbiased and accurate cell type annotations by ensuring the specificity of marker genes across cell clusters and types. It can also distinguish between healthy and malignant cell populations based on single-nucleotide variant calling.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Patrick L. Collins, Marina Cella, Sofia I. Porter, Shasha Li, Greer L. Gurewitz, Henoch S. Hong, R. Paul Johnson, Eugene M. Oltz, Marco Colonna
Article
Immunology
Emma R. Dorris, Simon J. Tazzyman, John Moylett, Nandhini Ramamoorthi, Jason Hackney, Michael Townsend, Munitta Muthana, Myles J. Lewis, Costantino Pitzalis, Anthony G. Wilson
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Jason P. Twohig, Ana Cardus Figueras, Robert Andrews, Florian Wiede, Benjamin C. Cossins, Alicia Derrac Soria, Myles J. Lewis, Michael J. Townsend, David Millrine, Jasmine Li, David G. Hill, Javier Uceda Fernandez, Xiao Liu, Barbara Szomolay, Christopher J. Pepper, Philip R. Taylor, Costantino Pitzalis, Tony Tiganis, Nigel M. Williams, Gareth W. Jones, Simon A. Jones
Article
Immunology
Marina Cella, Ramya Gamini, Cristiane Secca, Patrick L. Collins, Shanrong Zhao, Vincent Peng, Michelle L. Robinette, Jorge Schettini, Konstantin Zaitsev, William Gordon, Jennifer K. Bando, Kentaro Yomogida, Victor Cortez, Catrina Fronick, Robert Fulton, Lih-Ling Lin, Susan Gilfillan, Richard A. Flavell, Liang Shan, Maxim N. Artyomov, Michael Bowman, Eugene M. Oltz, Scott A. Jelinsky, Marco Colonna
Article
Cell Biology
Myles J. Lewis, Michael R. Barnes, Kevin Blighe, Katriona Goldmann, Sharmila Rana, Jason A. Hackney, Nandhini Ramamoorthi, Christopher R. John, David S. Watson, Sarah K. Kummerfeld, Rebecca Hands, Sudeh Riahi, Vidalba Rocher-Ros, Felice Rivellese, Frances Humby, Stephen Kelly, Michele Bombardieri, Nora Ng, Maria DiCicco, Desiree van der Heijde, Robert Landewe, Annette van der Helm-van Mil, Alberto Cauli, Iain B. McInnes, Christopher D. Buckley, Ernest Choy, Peter C. Taylor, Michael J. Townsend, Costantino Pitzalis
Article
Biology
Eugene Park, Swapneel Patel, Qiuling Wang, Prabhakar Andhey, Konstantin Zaitsev, Sophia Porter, Maxwell Hershey, Michael Bern, Beatrice Plougastel-Douglas, Patrick Collins, Marco Colonna, Kenneth M. Murphy, Eugene Oltz, Maxim Artyomov, L. David Sibley, Wayne M. Yokoyama
Article
Rheumatology
Gloria Lliso-Ribera, Frances Humby, Myles Lewis, Alessandra Nerviani, Daniele Mauro, Felice Rivellese, Stephen Kelly, Rebecca Hands, Fabiola Bene, Nandhini Ramamoorthi, Jason A. Hackney, Alberto Cauli, Ernest H. Choy, Andrew Filer, Peter C. Taylor, Iain McInnes, Michael J. Townsend, Costantino Pitzalis
ANNALS OF THE RHEUMATIC DISEASES
(2019)
Article
Immunology
Qianli Wang, Michelle L. Robinette, Cyrielle Billon, Patrick L. Collins, Jennifer K. Bando, Jose Luis Fachi, Cristiane Secca, Sofia I. Porter, Ankita Saini, Susan Gilfillan, Laura A. Solt, Erik S. Musiek, Eugene M. Oltz, Thomas P. Burris, Marco Colonna
SCIENCE IMMUNOLOGY
(2019)
Article
Cell Biology
Madison R. Mack, Jonathan R. Brestoff, Melissa M. Berrien-Elliott, Anna M. Trier, Ting-Lin B. Yang, Matthew McCullen, Patrick L. Collins, Haixia Niu, Nancy D. Bodet, Julia A. Wagner, Eugene Park, Amy Z. Xu, Fang Wang, Rebecca Chibnall, M. Laurin Council, Carrie Heffington, Friederike Kreisel, David J. Margolis, David Sheinbein, Paola Lovato, Eric Vivier, Marina Cella, Marco Colonna, Wayne M. Yokoyama, Eugene M. Oltz, Todd A. Fehniger, Brian S. Kim
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Cell Biology
Luz D. Orozco, Hsu-Hsin Chen, Christian Cox, Kenneth J. Katschke, Rommel Arceo, Carmina Espiritu, Patrick Caplazi, Sarajane Saturnio Nghiem, Ying-Jiun Chen, Zora Modrusan, Amy Dressen, Leonard D. Goldstein, Christine Clarke, Tushar Bhangale, Brian Yaspan, Marion Jeanne, Michael J. Townsend, Menno van Lookeren Campagne, Jason A. Hackney
Article
Biochemistry & Molecular Biology
Cesar A. Corzo, Eugene Varfolomeev, A. Francesca Setiadi, Ross Francis, Sha Klabunde, Kate Senger, Swathi Sujatha-Bhaskar, Joy Drobnick, Steven Do, Eric Suto, Zhiyu Huang, Jeffrey Eastham-Anderson, Arna Katewa, Jodie Pang, Melanie Domeyer, Christopher Dela Cruz, Andres Paler-Martinez, Vivian W. C. Lau, Azadeh Hadadianpour, Vladimir Ramirez-Carrozi, Yonglian Sun, Katherine Bao, Daqi Xu, Emily Hunley, Hans D. Brightbill, Soren Warming, Merone Roose-Girma, Alfred Wong, Lucinda Tam, Claire L. Emson, James J. Crawford, Wendy B. Young, Rajita Pappu, Brent S. McKenzie, Vida Asghari, Domagoj Vucic, Jason A. Hackney, Cary D. Austin, Wyne P. Lee, Annemarie Lekkerkerker, Nico Ghilardi, Marian C. Bryan, James R. Kiefer, Michael J. Townsend, Ali A. Zarrin
Article
Multidisciplinary Sciences
Patrick L. Collins, Caitlin Purman, Sofia Porter, Vincent Nganga, Ankita Saini, Katharina E. Hayer, Greer L. Gurewitz, Barry P. Sleckman, Jeffrey J. Bednarski, Craig H. Bassing, Eugene M. Oltz
NATURE COMMUNICATIONS
(2020)
Article
Immunology
Maria Tokuyama, Bronwyn M. Gunn, Arvind Venkataraman, Yong Kong, Insoo Kang, Tasfia Rakib, Michael J. Townsend, Karen H. Costenbader, Galit Alter, Akiko Iwasaki
Summary: In this study, elevated expression of an endogenous retrovirus ERV-K102, encoding an envelope protein, was observed in the blood of SLE patients, correlating with autoantibody levels and higher interferon status. Induction of ERV-K102 in SLE was negatively correlated with the expression of epigenetic silencing factors. Anti-ERV-K102 IgG levels in SLE plasma correlated with higher interferon stimulated gene expression, and promoted enhanced neutrophil phagocytosis of ERV-K102 envelope protein through immune complex formation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Vincent Peng, Xiaoyun Xing, Jennifer K. Bando, Tihana Trsan, Blanda Di Luccia, Patrick L. Collins, Daofeng Li, Wei-Le Wang, Hyung Joo Lee, Eugene M. Oltz, Ting Wang, Marco Colonna
Summary: This study characterizes the whole-genome distribution of DNA methylation and hydroxymethylation in innate lymphocytes. It identifies differentially methylated and hydroxymethylated regions between NK cells, ILC2s, and ILC3s and correlates them with transcriptional signatures. The study also reveals unique patterns of DNA methylation/hydroxymethylation in relation to open chromatin regions, histone modifications, and TF-binding sites.
Article
Oncology
Marcelo S. F. Pereira, Kinnari Sorathia, Yasemin Sezgin, Aarohi Thakkar, Colin Maguire, Patrick L. L. Collins, Bethany L. L. Mundy-Bosse, Dean A. A. Lee, Meisam Naeimi Kararoudi
Summary: Loss of cytotoxicity and defective metabolism in NK cells from AML patients or healthy donors with IL-15 expansion ex vivo are associated with GSK3 beta overexpression. Inhibition of GSK3 beta improves the function of these NK cells. This study reveals that GSK3 beta deletion does not affect cytotoxicity or maturation, but affects rRNA processing, cell proliferation, and metabolic function, suggesting a potential role of GSK3 beta in metabolic reprogramming of NK cells.
