It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease DOI Open Access
Amelia Cephas, William L. Hwang, Anirban Maitra

et al.

Gut, Journal Year: 2023, Volume and Issue: 72(6), P. 1211 - 1219

Published: March 30, 2023

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult study organs, such as pancreas. With advent these technologies approaches, field has grown, just a few years, from profiling pancreas disease states identifying molecular mechanisms therapy resistance pancreatic ductal adenocarcinoma, particularly deadly cancer. Single-cell transcriptomics related spatial approaches identified previously undescribed epithelial stromal cell types states, how populations change with progression, potential action which will serve basis for designing new therapeutic strategies. Here, we review recent literature on transcriptomic changed understanding biology progression.

Language: Английский

Museum of spatial transcriptomics DOI Open Access
Lambda Moses, Lior Pachter

Nature Methods, Journal Year: 2022, Volume and Issue: 19(5), P. 534 - 546

Published: March 10, 2022

Language: Английский

Citations

734
What is a cell type and how to define it? DOI Creative Commons
Hongkui Zeng

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

Citations

286
The emerging landscape of spatial profiling technologies DOI
Jeffrey R. Moffitt, Emma Lundberg, Holger Heyn

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 741 - 759

Published: July 20, 2022

Language: Английский

Citations

279
Cellular anatomy of the mouse primary motor cortex DOI Creative Commons
Rodrigo Muñoz-Castañeda, Brian Zingg, Katherine S. Matho

et al.

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 159 - 166

Published: Oct. 6, 2021

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated interpreted

Language: Английский

Citations

200
High-throughput sequencing of single neuron projections reveals spatial organization in the olfactory cortex DOI Creative Commons
Yushu Chen, Xiaoyin Chen, Batuhan Başerdem

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(22), P. 4117 - 4134.e28

Published: Oct. 1, 2022

Language: Английский

Citations

79
Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges DOI Creative Commons

Mengnan Cheng,

Yujia Jiang, Jiangshan Xu

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2023, Volume and Issue: 50(9), P. 625 - 640

Published: March 27, 2023

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology, from the invention of microscope 350 years ago recent emergence single-cell sequencing, which scientific community has been able visualize at an unprecedented resolution. Most recently, Spatially Resolved Transcriptomics (SRT) technologies have filled gap probing spatial or even three-dimensional organization molecular foundation behind mysteries life, including origin different cellular populations developed totipotent cells human diseases. In this review, we introduce progress challenges on SRT perspectives bioinformatic tools, as well representative applications. With currently fast-moving promising results early adopted research projects, can foresee bright future such new tools understanding most profound analytical level.

Language: Английский

Citations

76
Multimodal mapping of cell types and projections in the central nucleus of the amygdala DOI Creative Commons
Yuhan Wang, Sabine Krabbe, Mark Eddison

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 20, 2023

The central nucleus of the amygdala (CEA) is a brain region that integrates external and internal sensory information executes innate adaptive behaviors through distinct output pathways. Despite its complex functions, diversity molecularly defined neuronal types in CEA their contributions to major axonal projection targets have not been examined systematically. Here, we performed single-cell RNA-sequencing (scRNA-seq) classify cell identified marker genes map location these using expansion-assisted iterative fluorescence situ hybridization (EASI-FISH). We developed new methods integrate EASI-FISH with 5-plex retrograde labeling determine spatial, morphological, connectivity properties ~30,000 neurons. Our study revealed spatiomolecular organization CEA, medial lateral associated families. also found long-range axon network from where target regions receive inputs multiple types. Axon collateralization was primarily among projections hindbrain targets, which are forebrain projections. This resource reports gene combinations for axon-projection types, will be useful selective interrogation populations diverse functions CEA.

Language: Английский

Citations

44
Whole-cortex in situ sequencing reveals input-dependent area identity DOI Creative Commons
Xiaoyin Chen, Stephan Fischer,

M. Rué

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: April 24, 2024

The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each characteristic cytoarchitecture1,2, connectivity3,4 and activity5,6, wired modular networks3,4,7. However, it remains unclear whether these spatial organizations reflected in transcriptomic signatures how such established development. Here we used BARseq, a high-throughput situ sequencing technique, to interrogate the 104 cell-type marker genes 10.3 million cells, including 4,194,658 neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering single revealed consistent previous single-cell RNA studies8,9. composition highly predictive area identity. Moreover, areas similar compositions types, which defined as modules, overlap connected, suggesting same organization both connectivity. To explore profiles depend on development, assessed distributions after neonatal binocular enucleation. Notably, enucleation caused shifting compositional visual towards neighbouring within module, peripheral inputs sharpen distinct identities modules. Enabled by high throughput, low cost reproducibility our study provides proof principle for use large-scale reveal brain-wide molecular architecture understand its

Language: Английский

Citations

21
Spatial Transcriptomics: Technical Aspects of Recent Developments and Their Applications in Neuroscience and Cancer Research DOI Creative Commons
Han‐Eol Park,

Song Hyun Jo,

Rosalind H. Lee

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(16)

Published: April 7, 2023

Spatial transcriptomics is a newly emerging field that enables high-throughput investigation of the spatial localization transcripts and related analyses in various applications for biological systems. By transitioning from conventional studies to "in situ" biology, can provide transcriptome-scale information. Currently, ability simultaneously characterize gene expression profiles cells relevant cellular environment paradigm shift studies. In this review, recent progress its neuroscience cancer are highlighted. Technical aspects existing technologies future directions new developments (as March 2023), computational analysis transcriptome data, application notes studies, discussions regarding multi-omics their expanding roles biomedical emphasized.

Language: Английский

Citations

40
Spatial transcriptomics for profiling the tropism of viral vectors in tissues DOI Creative Commons
Min Jee Jang, Gerard Michael Coughlin,

Cameron Jackson

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(9), P. 1272 - 1286

Published: Jan. 26, 2023

A barrier to advancing engineered adeno-associated viral vectors (AAVs) for precision access cell subtypes is a lack of high-throughput, high-resolution assays characterize in vivo transduction profiles. In this study, we developed an ultrasensitive, sequential fluorescence situ hybridization (USeqFISH) method spatial transcriptomic profiling endogenous and RNA with short barcode intact tissue volumes by integrating hydrogel-based clearing, enhanced signal amplification multiplexing using labeling. Using USeqFISH, investigated the subtype tropisms across mouse brain regions six systemic AAVs, including AAV-PHP.AX, new variant that transduces robustly efficiently neurons astrocytes. Here reveal distinct biases each AAV variant, bias AAV-PHP.N toward excitatory neurons. USeqFISH also enables pooled regulatory cargos, as show 13-variant pool microRNA target sites genomes. Lastly, demonstrate potential applications multimodal single-cell analysis non-human primates.

Language: Английский

Citations

33