Radar helps ships navigate in fog and airplanes in bad weather. Without it, humans cannot see through the mist of the unknown, let alone traverse uncharted territories. The same goes for exploring life – a similar tool is needed to unveil the fundamentals of life.
A cell atlas created by single-cell technology, for assessing any type of cell in the organisms, especially mammals and primates, is such a tool. This was thoroughly discussed in a review published in the journal Life Medicine by authors from BGI-Research, which explains the importance of having such an atlas and what the biomedical field could gain from it.
The article “From monkey single-cell atlases into a broader biomedical perspective” is published in journal Life Medicine.
Why is a Single-Cell Atlas Important?
Cells are the basic building blocks of all living things. They are the fundamental units of a mammal, and their interactions orchestrate the complexity of life processes. To thoroughly understand the life cycle from birth to death, it is imperative to comprehend the biological and pathological dynamics across a variety of tissues. This comprehension is facilitated by the creation of extensive cell atlases using single-cell technology provided by leading genomics companies, such as BGI Group.
The generation of such atlases is vitally important for deepening our understanding of mammals. This significance arises not only from the inherent complexity of mammals, which poses challenges to biological understanding, but also from the potential these atlases hold to develop sophisticated diagnostic tools and disease-specific treatments.
Previous large-scale science projects have paved the way for single-cell sequencing. The Human Cell Atlas Consortium has accumulated a great quantity of data detailing the transcriptomics of individual cells, derived from extensive analyses of key human tissues and organs. Additionally, researchers have developed comprehensive atlases detailing the transcriptome and chromatin accessibility in mice and humans at all body tissue levels. These studies have enriched our understanding of the cellular diversity within mammals, as well as the composition and function of different cell types in corresponding tissues.
One of the most notable achievements in this endeavor is the creation of an ultra-high-resolution single-cell transcriptome atlas of the cynomolgus macaque. This atlas, which encompasses 45 organs, obtains data from single-cell analysis of a total of 1.14 million cells and identifies 113 major cell types. Published in the reputable journal Nature, this BGI-Research-led study provides crucial and extensive reference data for research involving both humans and other primates.
Moreover, a single-cell atlas depicting 27 major tissues/organs of the mouse lemur (Microcebus murinus), a commonly used model species, has also been recently reported.
Graphic A: A variety of single-cell methods have been applied to construct single-cell atlases of mammals to reveal the cellular heterogeneity of corresponding cell types in different tissues. Graphic B: Potential future applications of monkey single-cell transcriptomic atlas.
What Does an Atlas and Single-Cell Technology Offer?
Cell atlases hold great potential to advance precision medicine, both in prevention and treatment, by establishing connections between human genetic traits and disease-associated cells.
Single-cell atlases have proven instrumental in the identification of new cell types, particularly rare ones. An example is a study that revealed 10 previously unknown or minimally characterized cell types and subtypes in the transcriptomic cell atlas of mouse lemur. Another research team discovered some precursor cells expressing stem cell markers within adult tissues, potentially providing a cell source for future organ and cell repair therapies.
Single-cell atlases suggest that primates are a more suitable subject to study human disease than mice. One study leveraging a single-cell atlas demonstrated that certain human neurological genetic traits or diseases are closely associated with the same cell type in humans and monkeys, but rarely linked to the corresponding cell type in mice. For instance, traits of schizophrenia showed strong association with cortical excitatory neurons in primates but not in mice.
Furthermore, single-cell atlases shed light on which cell types are more susceptible to specific diseases. A study revealed that a macaque cell atlas dataset can serve as a critical tool for examining cell vulnerability to diseases. This atlas was used to create a virus database encompassing 126 virus-susceptible cell types, providing insights into which cells are most likely to be infected by a specific virus.
Single-cell atlases have also contributed to unravelling the mysteries of aging. Detailed cellular atlases of the lungs and cardiovascular system in young and old cynomolgus macaques have been produced. These atlases highlighted processes linked with reduced cellular function during aging or decreased cellular self-defending capabilities. Simultaneously, these studies explored why older bodies are more prone to aging-related diseases and COVID-19.
Because of the similarity between the menstrual and ovarian cycles of human females and cynomolgus macaques, a single-cell transcriptomic atlas of ovarian aging in the macaque was generated. This study indicated that oxidative damage is a principal factor leading to an age-related decline in ovarian function. Additionally, single-cell transcriptome atlases on the aging process in arteries and the hippocampus have also been created.
Beyond associating human diseases with their respective genes, single-cell transcriptomic atlases also establish links between genetic risk variants and cells potentially implicated in the expression of these variants at the RNA level.
The insights gained from cell atlases are invaluable for studies pertaining to drug evaluation and screening, aiding the development of targeted drugs, and supplying essential resources and tools for the creation of new biomedicines.
The Future of the Single-Cell Atlas
Given the current achievements of single-cell atlases, this review anticipates that future projects will uncover more intricate cell types and states. These projects will encompass all tissues and organs, and will potentially be applicable to a greater variety of species.
In the near future, single-cell atlases are expected to not only discover and characterize previously unrecognized cell types, but also shed light on the development stages of cells. This will facilitate a deeper understanding of cellular growth, migration, and interactions, and will assist in delineating how various cell types function and respond to the disruption from diseases.
One specific application lies in the realm of cancer treatment. Single-cell technology could be utilized to monitor cancer progression, treatment efficacy, and prognosis, and to identify therapeutic targets that could guide clinical drug administration.
Another prospective area of focus is neurological and neuropsychiatric disorders. Considering the numerous genes involved in brain development and the wide array of variants tied to the psychosis spectrum, applying single-cell methods to studying induced pluripotent stem cells derived from patients could reveal insights on the molecular level that may influence treatment strategies. This approach could provide a more sophisticated level of detail than traditional next-generation sequencing.
However, the limitations of single-cell technology should not be overlooked. When cells are isolated from their natural environments, they lose the ability to interact with surrounding cells, making it challenging to study how they work together. Fortunately, the advent of spatial transcriptomics technologies, such as BGI’s Stereo-seq, allows scientists to have a better picture of the location and activity of different cells. This offers scientists a more comprehensive view of how various cell types are distributed across different species.
Life Medicine: From monkey single-cell atlases into a broader biomedical perspective
BGI Group: International Team Led by BGI Completes First Whole-Body Cell Atlas of a Non-Human Primate