Four applications of single cell sequencing

Posted by beauty33 on December 29th, 2019

From the emerge of single-cell sequencing technology to today, it has achieved rapid development and remarkable results.

1. 1.Application in tumor research

On March, 2012, BGI Research Institute made breakthrough progress in cancer research, and published two research papers in Cell. This study develops a new method for analyzing single-cell genomes and applies the method to the genetic inheritance of tumors in primary thrombocytosis (a type of blood cancer) and renal clear cell carcinoma (a type of renal cancer). This new method solves the problem of high heterogeneity of tumors that could not be solved before, and provides new research ideas and opens up new research directions for in-depth study of cancer occurrence, development mechanism, diagnosis and treatment.

In 2016, researchers at the Massachusetts General Hospital's MGH and Broad Institute performed genome analysis of brain tumors at the single-cell level, and for the first time identified cancer stem cells and their differentiated offspring in human brain tumor samples. Researchers analyzed more than 4,000 tumor cells from six early oligodendroglioma samples and found that tumor cells can be divided into three types in development. One type is more like neural stem cells, and the other two have certain differentiation characteristics. The results confirm that cancer stem cells are the main growth source of oligodendrocyte tumors, and these cells will become promising therapeutic targets.

2. 2.Application in microbiology research

Single-cell sequencing has also made important breakthroughs in the field of microorganisms. In 2017, a research group from the United States UCSF realized the first prokaryotic microbial single-cell sequencing technology.

3. 3.Applications in neuroscience

Single-cell sequencing technology helps scientists better understand brain nerve cells. In 2017, a team led by the Salk Biological Institute distinguished neuron subtypes in mouse and human brain samples based on methylation and regulatory characteristics, and identified a new set of neurons in the human frontal cortex. The researchers used single-cell methylation sequencing to analyze nearly 6,200 neurons in mouse and human frontal cortex samples, and cluster known neuron subtypes based on methylation and regulatory element characteristics. In addition, they point out that there is a new neuron subtype in the human brain called "Layer 6 Excitatory Neurons", which has unique methylation markers.

Margarita Behrens, a computational neurobiology researcher at the Salk Institute and one of the authors of the paper, said: "Our research shows that we can clearly define neuron types based on their methylation groups. This helps us understand why two neurons with similar appearances in the same area behave differently. "

At the beginning of 2018, Professor Zhang Ye's team published a second-generation single-cell map of the adult brain based on a new single-cell nuclear sequencing method on Nature Biotechnology. By combining microfluidics-based single-nucleus sequencing (snDrop-seq) and single-cell transposon hypersensitivity site sequencing (scTHS-seq), this study not only can use transcriptomics analysis to identify cell types with different functions. It is also possible to better describe how these expression profiles are regulated or maintained through epigenetic characteristics. The study examined more than 60,000 single cells from the adult cerebral cortex and cerebellum, and found 35 different neuron and glial cell subtypes. We also discovered which subtypes of these cells are more susceptible to common risk factors for different brain diseases.

4. 4.Application in immunology

Because traditional immune cell analysis methods take samples from a large number of cells and underestimate the diversity of individual immune cells, we need to more accurately detect the genetic material of individual immune cells in order to understand the body's complex immune mechanisms.

In 2017, the Ido Amit team discovered a new type of immune cells in the brain, disease-associated microglia (DAM), which confirmed that DAM cells are responsible for degrading dead cells and protein lesions associated with Alzheimer's disease. The researchers emphasized that only RNA sequencing of a single cell could reveal rare microglia, which could provide new methods for treating neurological diseases, including Alzheimer's disease.

In 2017, scientists from institutions such as the Broad Institute identified new types of cells in the human immune system using single-cell genomics technology. They sequenced approximately 2400 single-cell RNA isolated from healthy blood donors and enriched the HLA-DR cell line in an attempt to re-identify and revise the classification of DC cells and monocytes. This result is one of the first important discoveries of the Human Cell Atlas project. The plan is to describe every cell in the human body with a view to accelerating the development of biomedicine and will revolutionize how doctors and researchers understand, diagnose and treat diseases.