Mapping the developing human immune system across organs

Area of Science:

• Developmental biology
• Immunology
• Genomics

Background:

• Previous single-cell studies mapped immune cells in specific prenatal organs.
• These studies were limited in depicting the immune system as a distributed network across tissues.

Purpose of the Study:

• To reconstruct the developing human immune system as a distributed network.
• To characterize immune cell development and function in prenatal tissues.

Main Methods:

• Profiling nine prenatal tissues using single-cell RNA sequencing.
• Utilizing antigen-receptor sequencing and spatial transcriptomics.
• Integrating multi-omic data for system-wide reconstruction.

Main Results:

• Identified late acquisition of immune-effector functions by myeloid and lymphoid cells.
• Revealed maturation of monocytes and T cells prior to peripheral tissue seeding.
• Uncovered prenatal immune cell development beyond primary hematopoietic organs, including human B1 cells and unconventional T cell origins.

Conclusions:

• The developed atlas provides comprehensive data and biological insights into the prenatal immune system.
• Findings facilitate advancements in cell engineering, regenerative medicine, and disease understanding.
• Highlights the importance of a systems-level approach to studying immune development.