Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

Elisa Lenti, Luca Genovese, Silvia Bianchessi, Aurora Maurizio, Simona Baghai Sain, Alessia di Lillo, Greta Mattavelli, Itamar Harel, Francesca Bernassola, Thomas Hehlgans, Klaus Pfeffer, Mariacristina Crosti, Sergio Abrignani, Sylvia M. Evans, Giovanni Sitia, Nuno Guimarães-Camboa, Vincenzo Russo, Serge A. van de Pavert, Jose Manuel Garcia-Manteiga, Andrea Brendolan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Lymph node (LN) stromal cells play a crucial role in LN 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 LN 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 LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.

Original languageAmerican English
Pages (from-to)606-622.e6
Issue number4
StatePublished - 12 Apr 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.


  • fibroblastic reticular cell
  • follicular dendritic cell
  • lineage tracing
  • lymph node development
  • marginal reticular cell
  • perivascular cell
  • single cell RNA-seq


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