Cargando…

Single-cell-level spatial gene expression in the embryonic neural differentiation niche

With the rapidly increasing availability of high-throughput in situ hybridization images, how to effectively analyze these images at high resolution for global patterns and testable hypotheses has become an urgent challenge. Here we developed a semi-automated image analysis pipeline to analyze in si...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Yi, Yu, Xiaoming, Sun, Na, Qiao, Nan, Cao, Yaqiang, Boyd-Kirkup, Jerome D., Shen, Qin, Han, Jing-Dong J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381528/
https://www.ncbi.nlm.nih.gov/pubmed/25575549
http://dx.doi.org/10.1101/gr.181966.114
_version_ 1782364469991571456
author Huang, Yi
Yu, Xiaoming
Sun, Na
Qiao, Nan
Cao, Yaqiang
Boyd-Kirkup, Jerome D.
Shen, Qin
Han, Jing-Dong J.
author_facet Huang, Yi
Yu, Xiaoming
Sun, Na
Qiao, Nan
Cao, Yaqiang
Boyd-Kirkup, Jerome D.
Shen, Qin
Han, Jing-Dong J.
author_sort Huang, Yi
collection PubMed
description With the rapidly increasing availability of high-throughput in situ hybridization images, how to effectively analyze these images at high resolution for global patterns and testable hypotheses has become an urgent challenge. Here we developed a semi-automated image analysis pipeline to analyze in situ hybridization images of E14.5 mouse embryos at single-cell resolution for more than 1600 telencephalon-expressed genes from the Eurexpress database. Using this pipeline, we derived the spatial gene expression profiles at single-cell resolution across the cortical layers to gain insight into the key processes occurring during cerebral cortex development. These profiles displayed high spatial modularity in gene expression, precisely recapitulated known differentiation zones, and uncovered additional unknown transition zones or cellular states. In particular, they revealed a distinctive spatial transition phase dedicated to chromatin remodeling events during neural differentiation, which can be validated by genomic clustering patterns, epigenetic modifications switches, and network modules. Our analysis further revealed a role of mitotic checkpoints during spatial gene expression state transition. As a novel approach to analyzing at the single-cell level the spatial modularity, dynamic trajectory, and transient states of gene expression during embryonic neural differentiation and to inferring regulatory events, our approach will be useful and applicable in many different systems for understanding the dynamic differentiation processes in vivo and at high resolution.
format Online
Article
Text
id pubmed-4381528
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-43815282015-10-01 Single-cell-level spatial gene expression in the embryonic neural differentiation niche Huang, Yi Yu, Xiaoming Sun, Na Qiao, Nan Cao, Yaqiang Boyd-Kirkup, Jerome D. Shen, Qin Han, Jing-Dong J. Genome Res Method With the rapidly increasing availability of high-throughput in situ hybridization images, how to effectively analyze these images at high resolution for global patterns and testable hypotheses has become an urgent challenge. Here we developed a semi-automated image analysis pipeline to analyze in situ hybridization images of E14.5 mouse embryos at single-cell resolution for more than 1600 telencephalon-expressed genes from the Eurexpress database. Using this pipeline, we derived the spatial gene expression profiles at single-cell resolution across the cortical layers to gain insight into the key processes occurring during cerebral cortex development. These profiles displayed high spatial modularity in gene expression, precisely recapitulated known differentiation zones, and uncovered additional unknown transition zones or cellular states. In particular, they revealed a distinctive spatial transition phase dedicated to chromatin remodeling events during neural differentiation, which can be validated by genomic clustering patterns, epigenetic modifications switches, and network modules. Our analysis further revealed a role of mitotic checkpoints during spatial gene expression state transition. As a novel approach to analyzing at the single-cell level the spatial modularity, dynamic trajectory, and transient states of gene expression during embryonic neural differentiation and to inferring regulatory events, our approach will be useful and applicable in many different systems for understanding the dynamic differentiation processes in vivo and at high resolution. Cold Spring Harbor Laboratory Press 2015-04 /pmc/articles/PMC4381528/ /pubmed/25575549 http://dx.doi.org/10.1101/gr.181966.114 Text en © 2015 Huang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Huang, Yi
Yu, Xiaoming
Sun, Na
Qiao, Nan
Cao, Yaqiang
Boyd-Kirkup, Jerome D.
Shen, Qin
Han, Jing-Dong J.
Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title_full Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title_fullStr Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title_full_unstemmed Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title_short Single-cell-level spatial gene expression in the embryonic neural differentiation niche
title_sort single-cell-level spatial gene expression in the embryonic neural differentiation niche
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381528/
https://www.ncbi.nlm.nih.gov/pubmed/25575549
http://dx.doi.org/10.1101/gr.181966.114
work_keys_str_mv AT huangyi singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT yuxiaoming singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT sunna singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT qiaonan singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT caoyaqiang singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT boydkirkupjeromed singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT shenqin singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche
AT hanjingdongj singlecelllevelspatialgeneexpressionintheembryonicneuraldifferentiationniche