Article
Genetics & Heredity
Lijiang Fei, Haide Chen, Lifeng Ma, Weigao E, Renying Wang, Xing Fang, Ziming Zhou, Huiyu Sun, Jingjing Wang, Mengmeng Jiang, Xinru Wang, Chengxuan Yu, Yuqing Mei, Danmei Jia, Tingyue Zhang, Xiaoping Han, Guoji Guo
Summary: Single-cell RNA-sequencing of mouse developmental stages reveals lineage-specific and shared regulatory programs controlling cell-fate decisions. Cross-species analysis links differentiation potency with ribosomal protein gene expression and identifies Xbp1 as a conserved regulator of cell-fate determinations. These findings provide genetic and molecular insights into cellular gene-regulatory programs and contribute to the understanding of cell-fate decisions.
Article
Multidisciplinary Sciences
Hailing Shi, Yichun He, Yiming Zhou, Jiahao Huang, Kamal Maher, Brandon Wang, Zefang Tang, Shuchen Luo, Peng Tan, Morgan Wu, Zuwan Lin, Jingyi Ren, Yaman Thapa, Xin Tang, Ken Y. Chan, Benjamin E. Deverman, Hao Shen, Albert Liu, Jia Liu, Xiao Wang
Summary: Spatially charting molecular cell types in the central nervous system of adult mice, this study creates a high-resolution molecular atlas and identifies previously unknown tissue architectures.
Article
Multidisciplinary Sciences
Yang Eric Li, Sebastian Preissl, Xiaomeng Hou, Ziyang Zhang, Kai Zhang, Yunjiang Qiu, Olivier B. Poirion, Bin Li, Joshua Chiou, Hanqing Liu, Antonio Pinto-Duarte, Naoki Kubo, Xiaoyu Yang, Rongxin Fang, Xinxin Wang, Jee Yun Han, Jacinta Lucero, Yiming Yan, Michael Miller, Samantha Kuan, David Gorkin, Kyle J. Gaulton, Yin Shen, Michael Nunn, Eran A. Mukamel, M. Margarita Behrens, Joseph R. Ecker, Bing Ren
Summary: Recent studies have identified hundreds of neural cell types in different brain regions of mice and humans, but the transcriptional regulatory programs responsible for the unique identity and function of each cell type remain unknown. By analyzing the chromatin accessibility in individual nuclei from various brain regions, researchers have mapped candidate cis-regulatory DNA elements in distinct cell types, providing insights into the gene regulatory programs of the mammalian brain.
Article
Multidisciplinary Sciences
Jun Ding, Jian Ji, Zachary Rabow, Tong Shen, Jacob Folz, Christopher R. Brydges, Sili Fan, Xinchen Lu, Sajjan Mehta, Megan R. Showalter, Ying Zhang, Renee Araiza, Lynette R. Bower, K. C. Kent Lloyd, Oliver Fiehn
Summary: By studying the metabolome atlas of aging wildtype mouse brains, it was found that metabolites significantly differ between different brain regions or age groups, with no effect of sex on these differences. Metabolic pathways undergo changes during aging, and functionally related brain regions also show similarities in metabolism. As age increases, metabolic correlations decrease, and cross-region correlation patterns reflect decreased brain segregation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Paula Nieto, Marc Elosua-Bayes, Juan L. Trincado, Domenica Marchese, Ramon Massoni-Badosa, Maria Salvany, Ana Henriques, Juan Nieto, Sergio Aguilar-Fernandez, Elisabetta Mereu, Catia Moutinho, Sara Ruiz, Patricia Lorden, Vanessa T. Chin, Dominik Kaczorowski, Chia-Ling Chan, Richard Gallagher, Angela Chou, Ester Planas-Rigol, Carlota Rubio-Perez, Ivo Gut, Josep M. Piulats, Joan Seoane, Joseph E. Powell, Eduard Batlle, Holger Heyn
Summary: The tumor immune microenvironment plays a crucial role in cancer progression and treatment, but there is significant variation among patients, leading to a lack of precision in prognosis and treatment response markers. By generating a single-cell tumor immune atlas, researchers aim to provide a foundation for patient stratification based on immune cell compositions, and to use SPOTlight to enable in situ mapping of immune populations for digital pathology. This innovative approach is expected to advance current stratification methods for prognosis and immunotherapy in oncology.
Article
Biochemistry & Molecular Biology
Andreas Keller, Laura Groeger, Thomas Tschernig, Jeffrey Solomon, Omar Laham, Nicholas Schaum, Viktoria Wagner, Fabian Kern, Georges Pierre Schmartz, Yongping Li, Adam Borcherding, Carola Meier, Tony Wyss-Coray, Eckart Meese, Tobias Fehlmann, Nicole Ludwig
Summary: The updated resource provides sequencing data of 188 tissue samples from six humans and 58 samples from Tabula Muris collection, totaling 87,252 non-coding RNAs, to shed light on organ specificity in the non-coding transcriptome.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Immunology
Isabelle Serr, Maria Kral, Martin G. Scherm, Carolin Daniel
Summary: HIS mice with reprogrammed iPSCs offer a promising approach for personalized medicine and immunotherapies, enabling the study of Tregs and their role in immune activation and inhibition, thus providing insights for cancer treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alexandre P. Marand, Zongliang Chen, Andrea Gallavotti, Robert J. Schmitz
Summary: By analyzing single-cell genomics data from six maize organs, researchers identified cis-regulatory factors and trans-regulatory factors, revealing the crucial role of cell-type-specific regulatory elements in gene expression regulation, and developed the single-cell analysis software Socrates for studying cis-regulatory variation in various species.
Article
Multidisciplinary Sciences
Velina Kozareva, Caroline Martin, Tomas Osorno, Stephanie Rudolph, Chong Guo, Charles Vanderburg, Naeem Nadaf, Aviv Regev, Wade G. Regehr, Evan Macosko
Summary: The cerebellar cortex is a complex brain structure with diverse roles, including regional specialization of Purkinje neurons and more continuous molecular variation within different types of cerebellar interneurons. Furthermore, molecular layer interneurons were found to consist of two distinct types with differences in electrophysiological properties. This study provides a comprehensive cellular atlas of the cerebellar cortex and suggests a framework for defining brain cell types based on molecular, morphological, and physiological characteristics.
Article
Biochemistry & Molecular Biology
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Xiaojie Qiu, Jin Yang, Jiangshan Xu, Shijie Hao, Xin Wang, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Zhao Li, Yan Hong, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Yue Yuan, Xiaoyu Wei, Huiwen Zheng, Weimin Feng, Zhifeng Wang, Yang Liu, Zhaohui Wang, Yunzhi Yang, Haitao Xiang, Lei Han, Baoming Qin, Pengcheng Guo, Guangyao Lai, Pura Munoz-Canoves, Patrick H. Maxwell, Jean Paul Thiery, Qing-Feng Wu, Fuxiang Zhao, Bichao Chen, Mei Li, Xi Dai, Shuai Wang, Haoyan Kuang, Junhou Hui, Liqun Wang, Ji-Feng Fei, Ou Wang, Xiaofeng Wei, Haorong Lu, Bo Wang, Shiping Liu, Ying Gu, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Jan Mulder, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
Summary: Spatially resolved transcriptomic technologies enable us to study complex biological processes such as mammalian embryogenesis. However, current methods have limitations in resolution, gene capture, and field of view, which hinders their systematic application to large and three-dimensional mid- and late-gestation embryos. In this study, we developed Stereo-seq, a spatially enhanced resolution omics-sequencing method, by combining DNA nanoball-patterned arrays and in situ RNA capture. We used Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas, MOSTA, which provides single cell resolution and high sensitivity for mapping the kinetics and directionality of transcriptional variation during mouse organogenesis. By utilizing this atlas, we investigated the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues like the dorsal midbrain. Our panoramic atlas will facilitate in-depth research into long-standing questions about normal and abnormal mammalian development.
Article
Multidisciplinary Sciences
Hanqing Liu, Jingtian Zhou, Wei Tian, Chongyuan Luo, Anna Bartlett, Andrew Aldridge, Jacinta Lucero, Julia K. Osteen, Joseph R. Nery, Huaming Chen, Angeline Rivkin, Rosa G. Castanon, Ben Clock, Yang Eric Li, Xiaomeng Hou, Olivier B. Poirion, Sebastian Preissl, Antonio Pinto-Duarte, Carolyn O'Connor, Lara Boggeman, Conor Fitzpatrick, Michael Nunn, Eran A. Mukamel, Zhuzhu Zhang, Edward M. Callaway, Bing Ren, Jesse R. Dixon, M. Margarita Behrens, Joseph R. Ecker
Summary: The study comprehensively assessed the epigenomes of different cell types in the mouse brain, revealing the diversity and spatial organization of cell types, as well as the repetitive usage of regulators for distinguishing cell subtypes. By constructing an artificial neural network model, it is possible to accurately predict the cell type and spatial location of individual neurons in the brain.
Article
Multidisciplinary Sciences
Mehmet Neset ozel, Felix Simon, Shadi Jafari, Isabel Holguera, Yen-Chung Chen, Najate Benhra, Rana Naja El-Danaf, Katarina Kapuralin, Jennifer Amy Malin, Nikolaos Konstantinides, Claude Desplan
Summary: Deciphering neuronal diversity in the Drosophila optic lobe during pupal development reveals transient extrinsic neurons and dorsoventral asymmetry in visual circuits.
Article
Cell Biology
Ximena Ibarra-Soria, Elodie Thierion, Gi Fay Mok, Andrea E. Mu euro Nsterberg, Duncan T. Odom, John C. Marioni
Summary: The mammalian body plan is formed by the segmentation of the mesoderm into somites, which are transient embryonic structures. Through a genomic analysis, we studied the transcriptional and chromatin dynamics during somitogenesis, revealing an accelerated rate of somite differentiation as development progresses. We also identified a conserved maturation program followed by all somites, as well as differentiation programs in more developed embryos.
DEVELOPMENTAL CELL
(2023)
Article
Pathology
Jenesis Gayden, Shikai Hu, Paul N. Joseph, Evan Delgado, Silvia Liu, Aaron Bell, Stephanie Puig, Satdarshan P. Monga, Zachary Freyberg
Summary: Hepatic zonation is crucial for liver function, and Wnt signaling plays a key role in this process. However, the expression of Wnt signaling components, particularly all 10 Frizzled receptors, in adult liver has not been fully characterized. In this study, the spatial expression of Fzd receptors was mapped in adult mouse liver, revealing that Fzd receptors 1, 4, and 6 were the most highly expressed. While most Wnt signaling occurred in zone 3, the expression of Fzd receptors did not show zonation. However, Fzd receptor 6 was preferentially expressed in zone 1. The study also showed that Fzd receptors and Wnts were not uniformly expressed by all hepatic cell types. These findings provide a foundation for future functional studies of Fzd receptors in healthy and diseased liver states.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Michael A. Skinnider, Nichollas E. Scott, Anna Prudova, Craig H. Kerr, Nikolay Stoynov, R. Greg Stacey, Queenie W. T. Chan, David Rattray, Jorg Gsponer, Leonard J. Foster
Summary: This study mapped the interactomes of seven mouse tissues using a novel quantitative proteomic approach, revealing the rewiring of protein interactions and their implications in cellular mechanisms and diseases. The findings open new avenues for understanding regulatory mechanisms shaping interactome responses in mammalian systems.
Editorial Material
Immunology
Julie Tellier, Stephen L. Nutt
Article
Oncology
Livius Penter, Elisa ten Hacken, Jackson Southard, Caleb A. Lareau, Leif S. Ludwig, Shuqiang Li, Donna S. Neuberg, Kenneth J. Livak, Catherine J. Wu
Summary: Murine models are essential for functional genomic studies and preclinical testing. A study using mtscATAC-seq technology on murine cancer models found mtDNA mutations and provided insights into disease biology and therapeutic vulnerabilities. This demonstrates the feasibility and utility of multi-modal single-cell and natural barcoding approaches.
Article
Cell Biology
Wing Fuk Chan, Hannah D. Coughlan, Michelle Ruhle, Nadia Iannarella, Carolina Alvarado, Joanna R. Groom, Christine R. Keenan, Andrew J. Kueh, Adam K. Wheatley, Gordon K. Smyth, Rhys S. Allan, Timothy M. Johanson
Summary: The transcription factor Myc is tightly regulated by the use of distal regulatory enhancers. In this study, a previously unidentified enhancer of Myc was discovered in activated B cells. However, genetic deletion of this enhancer had limited impact on Myc expression and cell proliferation. The findings highlight the complexity and dynamics of the regulation of critical genes like Myc.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Toshiki Yamada, Megumi Tatematsu, Shunsuke Takasuga, Akane Fuchimukai, Kenki Yamagata, Shinsuke Seki, Keiji Kuba, Hideyuki Yoshida, Ichiro Taniuchi, Gunter Bernhardt, Kazuko Shibuya, Akira Shibuya, Takechiyo Yamada, Takashi Ebihara
Summary: While group-2 innate lymphoid cells (ILC2s) are highly proliferative in allergic inflammation, the removal of overactivated ILC2s in allergic diseases has not been investigated. We previously showed that chronic airway allergy induces exhausted-like dysfunctional ILC2s expressing TIGIT. Chronic allergy stably induced TIGIT(+) ILC2s, which were highly activated, apoptotic, and were quickly removed from sites of chronic allergy. Our work demonstrates that TIGIT shifts the fate of ILC2s toward activation-induced cell death, which could present a new therapeutic target for chronic allergies.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Aidan M. Tousley, Maria Caterina Rotiroti, Louai Labanieh, Lea Wenting Rysavy, Won-Ju Kim, Caleb Lareau, Elena Sotillo, Evan W. Weber, Skyler P. Rietberg, Guillermo Nicolas Dalton, Yajie Yin, Dorota Klysz, Peng Xu, Eva L. de la Serna, Alexander R. Dunn, Ansuman T. Satpathy, Crystal L. Mackall, Robbie G. Majzner
Summary: Researchers have developed a new CAR T cell platform called LINK CAR, which replaces traditional CD3 zeta domains with intracellular proximal T cell signalling molecules. LINK CAR can activate T cells and eradicate tumors in vivo while bypassing certain upstream signalling proteins, showing superior efficacy and prevention of off-tumor toxicity compared to other systems. This study expands the range of molecules that can be targeted with CAR T cells, enabling their application in solid tumors, autoimmune diseases, and fibrosis, and also highlights the potential of repurposing cellular signaling machinery for cellular engineering.
Editorial Material
Biotechnology & Applied Microbiology
Caleb Lareau
Summary: SEACells can identify rare cell states in large datasets, enabling atlas-scale studies.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemical Research Methods
Caleb A. Lareau, Vincent Liu, Christoph Muus, Samantha D. Praktiknjo, Lena Nitsch, Pauline Kautz, Katalin Sandor, Yajie Yin, Jacob C. Gutierrez, Karin Pelka, Ansuman T. Satpathy, Aviv Regev, Vijay G. Sankaran, Leif S. Ludwig
Summary: The study developed a single-cell multi-omic approach called 'mtscATAC-seq' that enables simultaneous genotyping of mitochondrial DNA and profiling of accessible chromatin. By leveraging somatic mtDNA mutations, this method allows inference of clonal relationships among ex vivo-derived human cells. This technique provides a broadly applicable platform to map clonal relationships between cells in human tissues and enable additional modes of multi-omic discovery.
Review
Immunology
Minoru Matsumoto, Hideyuki Yoshida, Koichi Tsuneyama, Takeshi Oya, Mitsuru Matsumoto
Summary: The thymus is crucial for establishing self-tolerance by educating developing T-cells. Recent single-cell studies have revealed heterogeneity in medullary thymic epithelial cells (mTECs) and provided insights into the mechanisms underlying tissue-restricted antigen (TRA) expression. This overview highlights the role of Aire in inducing mTEC heterogeneity to encompass TRAs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Quynh P. Nguyen, Kennidy K. Takehara, Tianda Z. Deng, Shannon O'Shea, Maximilian Heeg, Kyla D. Omilusik, J. Justin Milner, Sara Quon, Matthew E. Pipkin, Jinyong Choi, Shane Crotty, Ananda W. Goldrath
Summary: After infection, T cells differentiate into long-lived memory cells that can circulate through secondary lymphoid organs or reside in tissues. CD4+ tissue-resident memory T cells (TRM) in the small intestine (SI) responding to acute viral infection share a gene expression program and chromatin accessibility profile with circulating TH1 cells, and gradually acquire a mature TRM program. Single-cell RNA sequencing reveals heterogeneity among established CD4+ TRM, predominantly located in the lamina propria, and identifies a population of cells that coexpress both effector- and memory-associated genes. Transcriptional regulators Blimp1, Id2, and Bcl6 are required for the formation and development of CD4+ TRM in the SI. These findings provide insights into the development, differentiation, and persistence of CD4+ TRM in response to viral infection.
SCIENCE IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nora Schmidt, Sabina Ganskih, Yuanjie Wei, Alexander Gabel, Sebastian Zielinski, Hasmik Keshishian, Caleb A. Lareau, Liv Zimmermann, Jana Makroczyova, Cadence Pearce, Karsten Krey, Thomas Hennig, Sebastian Stegmaier, Lambert Moyon, Marc Horlacher, Simone Werner, Jens Aydin, Marco Olguin-Nava, Ramya Potabattula, Anuja Kibe, Lars Doelken, Redmond P. Smyth, Neva Caliskan, Annalisa Marsico, Christine Krempl, Jochen Bodem, Andreas Pichlmair, Steven A. Carr, Petr Chlanda, Florian Erhard, Mathias Munschauer
Summary: Regulation of viral RNA biogenesis is crucial for SARS-CoV-2 infection. The host protein SND1 is identified to bind negatively-sense viral RNA and is essential for SARS-CoV-2 RNA synthesis. The viral protein NSP9 is covalently linked to the ends of viral RNA during infection and interacts with SND1 to initiate viral RNA synthesis.
Correction
Biotechnology & Applied Microbiology
Caleb A. Lareau, Leif S. Ludwig, Christoph Muus, Satyen H. Gohil, Tongtong Zhao, Zachary Chiang, Karin Pelka, Jeffrey M. Verboon, Wendy Luo, Elena Christian, Daniel Rosebrock, Gad Getz, Genevieve M. Boland, Fei Chen, Jason D. Buenrostro, Nir Hacohen, Catherine J. Wu, Martin J. Aryee, Aviv Regev, Vijay G. Sankaran
NATURE BIOTECHNOLOGY
(2023)
Article
Genetics & Heredity
Caleb A. Lareau, Sonia M. Dubois, Frank A. Buquicchio, Yu-Hsin Hsieh, Kopal Garg, Pauline Kautz, Lena Nitsch, Samantha D. Praktiknjo, Patrick Maschmeyer, Jeffrey M. Verboon, Jacob C. Gutierrez, Yajie Yin, Evgenij Fiskin, Wendy Luo, Eleni P. Mimitou, Christoph Muus, Rhea Malhotra, Sumit Parikh, Mark D. Fleming, Lena Oevermann, Johannes Schulte, Cornelia Eckert, Anshul Kundaje, Peter Smibert, Santosha A. Vardhana, Ansuman T. Satpathy, Aviv Regev, Vijay G. Sankaran, Suneet Agarwal, Leif S. Ludwig
Summary: This study establishes a multi-omics approach to quantify deletions in mtDNA in single cells and reveals the dynamics of pathogenic mtDNA deletion heteroplasmy consistent with purifying selection and distinct metabolic vulnerabilities across T-cell states.
Article
Immunology
Shengbo Zhang, Jai Rautela, Naiara G. Bediaga, Tatiana B. Kolesnik, Yue You, Junli Nie, Laura F. Dagley, Justin Bedo, Hanqing Wang, Li Sun, Robyn Sutherland, Elliot Surgenor, Nadia Iannarella, Rhys Allan, Fernando Souza-Fonseca-Guimaraes, Yi Xie, Qike Wang, Yuxia Zhang, Yuekang Xu, Stephen L. Nutt, Andrew M. Lew, Nicholas D. Huntington, Sandra E. Nicholson, Michael Chopin, Yifan Zhan
Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Meeting Abstract
Hematology
Kevin Nuno, Armon Azizi, Thomas Kohnke, Caleb Lareau, Asiri Ediwirickrema, Ryan Corces, Ravi Majeti
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Jacob M. Rosenberg, Joshua M. Peters, Travis Hughes, Caleb A. Lareau, Leif S. Ludwig, Lucas R. Massoth, Christina Austin-Tse, Heidi L. Rehm, Bryan Bryson, Yi-Bin Chen, Aviv Regev, Alex K. Shalek, Sarah M. Fortune, David B. Sykes
Summary: For patients with idiopathic aplastic anemia caused by STAT1 gene mutations, treatment with the JAK1 inhibitor itacitinib can rapidly resolve anemia and promote hematopoiesis recovery. Additionally, excessive activation of STAT1 may be a common feature among some idiopathic aplastic anemia patients.