- Suo, Chenqu;
- Dann, Emma;
- Goh, Issac;
- Jardine, Laura;
- Kleshchevnikov, Vitalii;
- Park, Jong-Eun;
- Botting, Rachel;
- Stephenson, Emily;
- Engelbert, Justin;
- Tuong, Zewen;
- Polanski, Krzysztof;
- Yayon, Nadav;
- Xu, Chuan;
- Suchanek, Ondrej;
- Elmentaite, Rasa;
- Domínguez Conde, Cecilia;
- He, Peng;
- Pritchard, Sophie;
- Miah, Mohi;
- Moldovan, Corina;
- Steemers, Alexander;
- Mazin, Pavel;
- Prete, Martin;
- Horsfall, Dave;
- Marioni, John;
- Clatworthy, Menna;
- Haniffa, Muzlifah;
- Teichmann, Sarah
Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.