| Table of Contents |
| |
|
|
|
|
| UTR-ly unexpected: RNA chaperones tame intrinsically disordered proteins |
| Miriam Linsenmeier, James Shorter |
| How do cells ensure that complex, multidomain proteins fold correctly? Luo et al. reveal a self-contained solution. The 3′UTR of an mRNA co-translationally chaperones the protein it encodes, preventing intrinsically disordered regions from making inappropriate contacts. This functionality, localized to mesh-like condensates, challenges Anfinsen’s dogma and opens therapeutic possibilities. |
|
|
| The silicon citizen naturalist |
| Matthew E. Hudson, Gopal Battu |
| Smartphone-wielding citizen scientists and an AI called FLORIST are transforming ecology at the continental scale. In this issue of Cell, when Tibbs-Cortes et al. pair the crowdsourced data with controlled genetics, they discover how switchgrass times its flowering to outwit both frost and heat, depending on latitude. |
|
|
|
|
| Do autoantibodies shape cancer immunosurveillance? |
| Paul Bastard, Tyler Hulett, Karl Smith-Byrne, Nils Landegren, Trine H. Mogensen, Jacques Fellay, Ruth C. Travis, Jean-Laurent Casanova, Chi V. Dang, Xin Lu |
| Why cancer arises, progresses, or proves fatal in some people but not others remains largely unresolved. Antibody repertoires, including autoantibodies targeting immune pathways, may shape cancer immunosurveillance. Mapping antibody landscapes across cancer-free, at-risk, and cancer-affected individuals could clarify their roles in cancer susceptibility and disease outcome. |
|
|
|
|
| Auxin signaling |
| Jiashu Chu, Aaron Chun Hou Ang, Martijn de Roij, Lucia Strader, Tongda Xu, Dolf Weijers |
| Open Access |
| The hormone auxin is central to plant growth and development. Auxin triggers slow nuclear gene-expression changes and fast cell-surface signaling within minutes. This review summarizes new mechanistic advances that reshape the classic view and link rapid and slow responses into a more integrated picture. |
|
|
|
|
| Genome instability triggers intercellular DNA transfer between human cells |
| Elizabeth G. Maurais, Alice Mazzagatti, Yu-Fen Lin, Maria Narozna, Qing Hu, Rashmi Dahiya, Derek Santiago-Ferrer, Conor P. Herlihy, Mary Krebs, Nikoleta Pateraki, Evlampia Parcharidou, Stamatis Papathanasiou, Brian J. Beliveau, Gary J. Gorbsky, Isidro Cortés-Ciriano, Peter Ly |
| Open Access |
| Mammalian cells can pass damaged pieces of their genome directly to neighboring cells via contact-dependent, nanotube-like connections. These transferred DNA fragments persist and function, revealing an unexpected route by which genome damage can propagate between cells. |
|
|
|
|
| Deep learning of functional perturbations from condensate morphology |
| Anita Donlic, Troy J. Comi, Sofia A. Quinodoz, Nima Jaberi-Lashkari, Krist Antunes Fernandes, Lifei Jiang, Lennard W. Wiesner, Ai Ing Lim, Clifford P. Brangwynne |
| Open Access |
| A deep learning method quantitatively decodes nucleolar, nuclear speckle, and viral condensate morphology to reveal underlying biochemical states. Applying this framework reveals a previously unrecognized role for TOP1 in ribosome biogenesis and nucleolar organization. |
|
|
|
|
| Uncovering spatially resolved functional genomics with CRISPR screen sequencing |
| Haorui Zhang, Zongxu Zhang, Peiyu Wang, Tian Xu, Xiaoyu Chen, Yanping Zhao, Siyu Lin, Wenjie Cai, Pengfei Ren, Ce Luo, Peng Zhang, Yunfeng Wang, Sen Hou, Yahui Zhao, Hu Zeng, Zhihua Liu, Cunyu Wang, Zhidong Gao, Yu Feng, Deng Pan, Zexian Zeng |
| Open Access |
| Zhang et al. present SPAC-seq, a sequencing-based spatial CRISPR screening technology capturing high-throughput perturbation libraries and spatial whole transcriptomes. Complementing this, TARDIS is developed as a statistical toolkit for spatial perturbation analysis. Together, they facilitate discoveries in spatial functional genomics, including cell localization, microenvironmental organization, pathway regulation, and ligand-receptor interactions. |
|
|
|
|
|
|
| Harnessing citizen science to contextualize adaptation mechanism discovery |
| Laura E. Tibbs-Cortes, Linqian Han, Jeremy B. Jewell, Puranjit Singh, Haiyan Huang, Ryan Benke, Tony Trieu, Zhou Tang, Soyeon Choi, Jianxin Zhao, Eudald Illa Berenguer, Thomas H. Pendergast IV, Bing Liu, Tina Le, Kankshita Swaminathan, Xiaoyu Weng, Carson Andorf, Michelle A. Graham, Karen Sanguinet, Zhiwu Zhang, Laura E. Bartley, Yin Bao, Wayne Parrott, Katrien M. Devos, Thomas Juenger, Jianming Yu, Xianran Li |
| Open Access |
| Juxtaposing citizen science in situ observations and designed ex situ experiments through identified major genetic and environmental determinants reveals mechanisms of adaptation that shape haplotype distribution across native habitats. |
|
|
| Continuous modeling of primate embryogenesis from totipotency to early organogenesis |
| Wei Zheng, Bing Peng, Zilin Chen, Kangwei Huang, Yueyao Qi, Huimin Niu, Hui Shen, Jun Wu, Jianwei Jiao, Peng Du |
| A primate embryoid system is established from cynomolgus totipotent blastomere-like cells. This fertilization-independent system recapitulates development from a totipotent-like state through an intermediate 8CMLC stage to early organogenesis with neural-tube-like structures and cardiac-like beating activity. |
|
|
| Two distinct causes contribute to the low efficiency of human pre-implantation development |
| Zixuan Li, Lizhi Leng, Jinglei Zhai, Xiaowen Wang, Wuling Yang, Shuhui Wang, Haifeng Wan, Shuoping Zhang, Fei Gong, Xi Liao, Yuhui Li, Qing Zeng, Yansu Chen, Zhenyu Xiang, Feiyao Liu, Fuchu He, Yun Yang, Hongmei Wang, Xiaoming Xu, Ge Lin, Chun So |
| Open Access |
| Live imaging covering the entire human pre-implantation development reveals that the second mitotic division is the most error-prone, where stochastic centriole overduplication predisposes 2-cell embryos to missegregating chromosomes and arresting before the 8-cell stage. By contrast, later embryonic arrest involves endoplasmic reticulum stress. |
|
|
| Arc mediates intercellular tau transmission via extracellular vesicles |
| Mitali Tyagi, Eric de Hoog, Matthew Grega, Kaelan R. Sullivan, Alicia C. Walker, Radhika Chadha, Ava Northrop, Balázs Fábián, Gerhard Hummer, Monika Fuxreiter, Bradley T. Hyman, Jason D. Shepherd |
| Open Access |
| Tau pathology spreads cell to cell in Alzheimer’s disease, but the molecular mechanisms are unclear. This study found that the capsid-forming protein Arc binds and packages tau into extracellular vesicles that are released from neurons, which eliminates toxic intracellular tau and promotes intercellular tau transmission. |
|
|
| TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy |
| Shuyi Zeng, Shenqing Zhang, Shengnan Zhang, Yun Fan, Wencheng Xia, Feiyang Chen, Chengan Huang, Shiran Lv, Jinxia Lu, Yunpeng Sun, Kaien Liu, Yunxia Li, Yaoyang Zhang, Jian Wang, Cong Liu, Dan Li |
| Characterization of TPPP/p25 amyloid aggregation enables the development of a seed amplification assay that distinguishes MSA from related neurodegenerative diseases and serves as a CSF MSA biomarker. |
|
|
| Physiological brain clearance architecture revealed by neuronal protein tracing |
| Yuichi Chayama, Nalini R. Rao, Daniela Perla, Zimo Zhang, Madigan Reid, Sophia Nelson, Xinlan Wen, Bella Ding, Jessica Blumenfeld, Amanda Apolonio, Sahith Doddipalli, Haoyue Zhou, Sena Gül Turhan, Pu-Yun Shih, Matthias Brendel, Ying-Hui Fu, Ali Ertürk, Zeynep Ilgin Kolabas, Yadong Huang, Andrew C. Yang |
| Open Access |
| Neuronal protein tracing, unlike CSF tracers, reveals that brain clearance follows a “nearest exit” principle through distinct border immune niches disrupted differently by disease. |
|
|
|
|
| Decoding the spatiotemporal development of human meninges |
| Yanxin Li, Zhongqiu Li, Yong She, Ziqing He, Changliang Wang, Yuehong Zhang, Rong Li, Lei Jin, Fen Ji, Peng Du, Ji Dong, Jianwei Jiao |
| A spatiotemporal atlas of the human meninges during early-to-mid gestation identifies asynchronous layer development and transcriptomic features of meningeal cells and demonstrates that pial fibroblasts recruit several meningeal macrophages via CXCL12-CXCR4 signaling to regulate Cajal-Retzius cell development. |
|
|
| Map of spiking activity underlying change detection in the mouse visual system |
| Corbett Bennett, Samuel D. Gale, Greggory Heller, Tamina K. Ramirez, Hannah Belski, Alex Piet, Omid Zobeiri, Adam Amster, Anton Arkhipov, Alex Cahoon, Shiella Caldejon, Mikayla Carlson, Linzy Casal, Scott F. Daniel, Colin Farrell, Marina Garrett, Ryan Gillis, Conor Grasso, Ben J. Hardcastle, Ross Hytnen, Tye Johnson, Peter Ledochowitsch, Quinn L’Heureux, Dana Mastrovito, Ethan G. McBride, Stefan Mihalas, Chris Mochizuki, Christopher B. Morrison, Chelsea Nayan, Nhan-Kiet Ngo, Kat North, Douglas R. Ollerenshaw, Ben Ouellette, Paul Rhoads, Kara Ronellenfitch, Martin Schroedter, Joshua H. Siegle, Cliff Slaughterbeck, David Sullivan, Jackie Swapp, Michael Taormina, Wayne Wakeman, Xana Waughman, Allison Williford, John W. Phillips, Peter A. Groblewski, Séverine Durand, Christof Koch, Shawn R. Olsen |
| Open Access |
| Large-scale Neuropixels recordings across the mouse visual system during an image-change detection task map how sensory, motor, and task engagement signals are distributed across the cortex, thalamus, and midbrain. Task and novelty signals differentially modulate activity along this hierarchy, and combined decoding and optogenetics suggest mice detect changes via an adaptation-based strategy within a critical time window. |
|
|
| Multimodal imaging of gene expression, morphology, and activity of the same neuron |
| Yuchen Zhao, Ziqi Shi, Xinglan Liu, Lin Cong, Peng Yu, Xiaoxue Shi, Lu Bai, Yujie Zhang, Liqin Gu, Xiaofei Wang, Chenxi Jin, Liuqin Qian, Wei Deng, Xinhe Zhang, Tielin Zhang, Ninglong Xu, Shengjin Xu, Kai Wang |
| This study establishes an imaging-based multimodal characterization (IMC) platform to link in vivo activity, whole-brain morphology, and spatial gene expression in the same cortical projection neurons. Applied to the mouse visual cortex, IMC reveals complementary morphological and molecular predictors of visual responses, identifies a neuronal subtype defined by trimodal profiling, and provides a ground-truth resource for multimodal integration. |
|
|
| Bacteriophage genome-wide transposon mutagenesis |
| Alex Chan, Wearn-Xin Yee, Deepto Mozumdar, Claire Kokontis, Matias Rojas-Montero, Miaoxi Liu, Ying Yang, Li Yuping, Joseph Bondy-Denomy |
| A technique enabling phage transposon mutagenesis and sequencing reveals previously unknown non-essential and fitness-conferring genes in both jumbo phages and base-modified phages. |
|
|
|
|
|
