Spatial Genomic Analysis: A Multiplexed Transcriptional Profiling Method that Reveals Subpopulations of Cells Within
Antti Lignell1, Laura Kerosuo2,3
1Single-Cell Quantitative Biology Lab, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Methods in Molecular Biology (Clifton, N.J.)
|September 9, 2018
Summary
Spatial Genomic Analysis (SGA) is a new method for single-cell gene expression profiling. This technique reveals previously unknown neural crest cell heterogeneity and gene relationships, advancing developmental biology research.
Area of Science:
- Developmental Biology
- Genomics
- Molecular Biology
Background:
- Neural crest cells are crucial for vertebrate development but their heterogeneity is poorly understood.
- Previous technical limitations hindered detailed analysis of neural crest cell populations.
- Understanding neural crest cell differentiation is key to developmental processes.
Purpose of the Study:
- To introduce Spatial Genomic Analysis (SGA), a novel method for quantitative single-cell transcriptional profiling.
- To investigate heterogeneity within the neural crest cell population.
- To identify molecular factors and gene relationships within individual neural crest cells.
Main Methods:
- Spatial Genomic Analysis (SGA) utilizes single-molecule imaging of individual transcripts for up to 100 genes.
- A machine learning-based image analysis pipeline performs robust cell segmentation and transcript counting.
- SGA is applied to analyze neural crest cell populations in situ.
Main Results:
- SGA successfully identified distinct subgroups within the neural crest niche.
- The method's high sensitivity enabled detection of low-expressed genes, including pluripotency and lineage markers.
- SGA provided predictions of gene relationships within individual cells.
Conclusions:
- Spatial Genomic Analysis (SGA) overcomes previous technical limitations in studying cell heterogeneity.
- SGA reveals novel molecular insights into neural crest cell development and differentiation.
- This method offers broad utility for advanced transcriptome analyses in various biological contexts.
Keywords:
Chicken embryoHCRHybridization chain reactionIn vivo single-cell analysisNeural crest stem cell nicheNeural crest stem cellsPluripotencyQuantitative single-molecule fluorescent in situ hybridizationSGASingle-molecule microscopySpatial genomic analysisSpatial genomicsSpatial tissue transcriptome analysissmFISHMore Related Videos
Related Concept Videos
02:35Transcription Elongation Factors
14.0K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
14.0K
01:10Transcription
156.7K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
156.7K
02:02Genomics
40.7K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.7K
02:16Transcription Factors
82.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.8K
02:13Cooperative Binding of Transcription Regulators
7.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.4K
02:23Master Transcription Regulators
7.8K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.8K