Atlas of the immune system development in the fetal blood

Unprecedent information have been obtained to understand the ontogeny of immune cells in lymph organs during early fetal development. However, little is known about immune cells and host factors in the blood. Here we generated the first comprehensive atlas of blood cells and proteins throughout the fetal development using the multiomics approaches. The temporal changes of blood cells play important roles in development and maturation of the fetal immune system. Some proteins in the blood are excellently correlated with gestation weeks. The gradual increases of CDR3 lengths over time through multiple pathwyas markedly increase the diversity of TCR and BCR repertoires. Our comprehensive atlas is highly valuable for understanding the development of fetal immune system and studying the disorders that associated with fetal immune system. Cell types, distributions and origins in early fetal tissues have been well studied using the single cell analysis approaches in recent years (1). Unprecedent data have been accumulated to comprehend the immune cell development in great details (2, 3). This has led to a much better understanding of ontogeny of immune cells in lymph organs and peripheral tissues during early fetal development. It is well established that yolk sac and the aorta gonad mesonephros (AGM) are the sources of immune cells, which subsequently seed into the liver, thymus and bone merrow, and finally reach to the peripheral organs (1). However, previous studies have focused on development of immune cells in the early stage (< 20 postconceptional weeks; pcw) of fetuses (1). The analyses were often limited by the small number of the cells available and only mRNA transcripts from single cells have been analyzed. The blood plays a critical role by transferring immune cells back and forth between lymph organs and peripheral tissues to ensure the normal development of the immune system. However, little is known about the status of the immune cells and host protein factors in the blood during the fetal development. Here, we performed multiomics analyses of individual blood cells and proteins as well as cell functions of blood cells after stimulation throughout the fetal development. These results allow us to comprehensively and systematically investigate the immune system in the fetal blood from the time when the blood circulation system become complete at 12 pcw to the near full term of pregnancy (39 pcw). These data together allowed us to generate a detailed atlas of immune system development in the fetal blood. Additional Note: We have provided a data visualization map, which can be accessed via the following link: Fetal single Cell Visualization Map Web