High-throughput single-cell RNA sequencing (scRNA-seq) made it possible to map single-cell transcriptomes at the organic level. Cell atlases have already been created for vertebrate and invertebrate systems. However, this research is still limited. They often relate only to a specific species or period, and therefore cannot be used to an in-depth comparison between different species and different tissues.
Professors Han Xiaoping and Guo Guoji, from Zhejiang University Medical School, led the team. The researchers have used Microwell-seq technology to profile different species at various life stages. These are more than 2.6 million single cells from mice, zebrafish and Drosophila. These data made it possible to construct an interspecies cellular landscape.
The three species studied show similarities throughout their life cycle
The study found that cells and genes change with development and age in mice, zebrafish and Drosophila. The proportions of immune cells and the inflammatory response of tissues increased gradually with age in all three species. Nevertheless, the mouse showed a decrease in the ratio of T cells, while B cells increased.
According to gene expression trajectories, all three species exhibit similarities throughout their life cycle. As they got older, immune responses increased, while pathways related to mitochondrial metabolism were reduced. Examination of transcription factor regulation showed that the same gene families were responsible for the adjustment of certain cell lines for the three species.
Pioglitazone would be able to attenuate the aging phenotype
According to the interspecies analysis, immune responses and mitochondrial functions would be linked to the aging process. The researchers studied the activity of transcription factors and the ratio between upregulated and downregulated genes. Some of these factors may be involved in immunity, lipid and energy metabolism. They would act as regulators in the aging process in several species.
The team treated two-year-old mice with pioglitazone (PGZ). It is a drug that the Food and Drug Administration (FDA) has approved. He seems to have attenuated the aging phenotype in mammals. Intrinsic regulatory networks would connect mitochondrial metabolism and inflammation due to aging. The treatment would have a positive effect on cell aging and lipid metabolism.