Single-Cell DNA Sequencing Service

Single-cell DNA sequencing is a high-resolution genomic technology that analyzes the DNA content of individual cells, providing insights into genetic variations such as single-nucleotide polymorphisms (SNPs), copy number variations (CNVs), and structural alterations. Single-cell DNA sequencing begins with environmental or tissue samples, followed by single-cell isolation using Laser Capture Microdissection (LCM), Fluorescence-Activated Cell Sorting (FACS), or microfluidics. DNA is then extracted and amplified through Multiple Displacement Amplification (MDA). The amplified DNA is used to construct sequencing libraries, which undergo high-throughput sequencing. Finally, bioinformatic analysis is performed to identify single nucleotide polymorphisms (SNPs), copy number variations (CNVs), and cell type information.

 



Chang-Hui, Shen. Diagnostic Molecular Biology. 2019.

Figure 1. The Workflow of Single-Cell DNA Sequencing

 

Unlike bulk sequencing, single-cell DNA sequencing reveals the heterogeneity within cell populations, which is critical for understanding complex biological systems. It is essential for studying tumor evolution, rare genetic mutations, and cellular lineage tracing. single-cell DNA sequencing addresses key challenges in identifying rare subpopulations and uncovering dynamic genomic changes in both healthy and diseased states, offering a precise approach to decoding cellular diversity.

 

Services at MtoZ Biolabs

MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider, provides advanced proteomics, metabolomics, and biopharmaceutical analysis services to researchers in biochemistry, biotechnology, and biopharmaceutical fields. MtoZ Biolabs offers professional single-cell DNA sequencing service powered by advanced third-generation sequencing platforms and high-resolution mass spectrometry systems, delivering high-sensitivity genomic analysis. Our team of experienced technical experts specializes in single-cell isolation, DNA extraction, amplification, and sequencing. With extensive project experience, we provide customized experimental design and comprehensive data analysis. Our end-to-end service includes sample preparation, library construction, sequencing, and bioinformatics, offering efficient solutions for life sciences and precision medicine research. Regarding DNA sequencing, we also offer the following services to meet the diverse needs of researchers:

1. Single-Cell Long Read Sequencing

2. Integrative Metabolomics-16S rDNA Sequencing Analysis Service

3. 16S/18S/ITS Amplicon Sequencing Service

4. Single-Cell Methylation Sequencing

5. Droplet-Based Single-Cell Sequencing

 

For more services, please contact us freely.

 

Service Advantages 

1. High-Resolution Genomic and Epigenomic Analysis  

Our single-cell DNA sequencing service provides precise insights into genomic variations, including copy number alterations, DNA methylation, and chromatin accessibility, enabling comprehensive studies of cellular function and regulation.  

 

2. Advanced Clonal Evolution and Lineage Tracing  

The single-cell DNA sequencing service facilitates the tracking of clonal evolution and lineage tracing, uncovering dynamic changes in cellular subpopulations and developmental trajectories across different biological systems.  

 

3. Integration of Spatially Resolved Analysis  

By combining spatially resolved sequencing technologies, our single-cell DNA sequencing service enhances the understanding of genetic variations within the spatial context of tissues, aiding in tissue-specific research.  

 

4. Utilization of Third-Generation Sequencing Technologies  

Leveraging cutting-edge third-generation sequencing platforms, the single-cell DNA sequencing service achieves long-read sequencing, enabling the detection of structural variations and complex genome architectures with exceptional accuracy.  

 

Case Study

1. Single-cell DNA Amplicon Sequencing Reveals Clonal Heterogeneity and Evolution in T-cell Acute Lymphoblastic Leukemia

This study employed single-cell targeted DNA amplicon sequencing to investigate clonal heterogeneity and evolution in T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and during treatment. The research analyzed 108,188 cells from 25 samples across 8 patients, covering 110 genes. Results revealed a major clone at diagnosis alongside minor clones, some constituting less than 1% of cells. Longitudinal analysis showed that minor clones at diagnosis could evolve into dominant clones, underscoring the importance of NOTCH1 and other mutations in T-ALL progression. Our single-cell DNA sequencing service facilitates precise analysis of clonal structures and dynamic changes across different stages of disease. It is designed to support research into genetic variation in complex biological systems.

 



Albertí-Servera, L, et al. Blood. 2021.

Figure 2. T-ALL Mutational Landscape Based on Single-Cell DNA Sequencing of 8 Pediatric Patients

 

2. Single-Cell DNA Sequencing Reveals Punctuated and Gradual Clonal Evolution in Hepatocellular Carcinoma

This study employed single-cell DNA sequencing to explore copy number alterations and clonal evolution in hepatocellular carcinoma (HCC). Analysis of 1275 cells from 10 patients revealed a dual-phase CNA evolution model, with a punctuated phase followed by a gradual phase. Tumors with prolonged gradual phases exhibited higher intratumor heterogeneity and worse disease-free survival. Integration of transcriptomic and immunohistochemical data identified CAD, a gene involved in pyrimidine synthesis, as a biomarker for rapid tumor progression. Additionally, ploidy-resolved scDNA-seq showed that polyploid tumor cells likely originated from whole-genome doubling of diploid tumor cells. The Single-cell DNA sequencing service provides advanced solutions for investigating genetic changes and clonal evolution in complex diseases like hepatocellular carcinoma. It supports research into copy number alterations, tumor heterogeneity, and molecular biomarkers.

 



Guo, L. et al. Gastroenterology. 2022.

Figure 3. Single-Cell DNA Sequencing Revealed the CNA Heterogeneity Landscape in 10 HCC Cases

 

Applications

1. Studying Somatic Mutations and Tumor Heterogeneity  

Our single-cell DNA sequencing service enables precise analysis of somatic mutations at the single-cell level, offering insights into tumor heterogeneity and clonal evolution. This service is ideal for exploring cancer initiation, progression, and mechanisms of treatment resistance, advancing personalized oncology.  

 

2. Deciphering Genomic Dynamics in Organismal Development  

With single-cell DNA sequencing service, researchers can track genomic changes in individual cells during development, revealing genetic and epigenetic mechanisms underlying cell division, differentiation, and organogenesis. This provides critical molecular insights for developmental biology and regenerative medicine.  

 

3. Microbial Population and Environmental Genomics  

Our single-cell DNA sequencing service facilitates genome sequencing of individual microorganisms in environmental samples, helping to uncover microbial diversity, evolutionary trajectories, and ecological functions. This opens new avenues for research in microbiology and environmental science.  

 

4. Reproductive Medicine and Genetic Disease Research  

Single-cell DNA sequencing service is applied in reproductive medicine to analyze genomic integrity at the single-cell level in gametes and embryos, identifying genetic abnormalities. Additionally, this service aids in studying rare genetic diseases, supporting advancements in genetic diagnostics and therapies.  

 

Deliverables

1. Comprehensive Experimental Details

2. Materials, Instruments, and Methods

3. Relevant Liquid Chromatography and Mass Spectrometry Parameters

4. The Detailed Information of Single-Cell DNA Sequencing

5. Mass Spectrometry Image

6. Raw Data