DESCRIPTION

Lymph node (LN) is like small bean structure that is part of the body's immune system.

They work like a filter of substances that travel through the lymphatic fluid, and they contain lymphocytes that help the body fight infection and disease.

There are hundreds of lymph nodes found in the human body.

LN stromal cells play a crucial role in Lymph node development and in supporting adaptive immune responses.

However, their origin, differentiation pathways, and transcriptional programs are still elusive.

Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of Lymph node stromal and endothelial progenitors.

Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6⁺ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3⁺ progenitors of the paraxial mesoderm (PXM).

Single-cell RNA sequencing revealed the existence of different Cd34⁺ and Cxcl13⁺ stromal cell subsets and showed that embryonic LN contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells.

Our work identifies the earliest embryonic sources of Lymph nodes stromal and endothelial cells and demonstrates that stromal diversity begins already during Lymph node development.

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