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

Autor: Lenti E; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Genovese L; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Bianchessi S; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Maurizio A; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Sain SB; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., di Lillo A; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Mattavelli G; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Harel I; Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel., Bernassola F; Department of Experimental Medicine, TOR, University of Rome 'Tor Vergata', Rome 00133, Italy., Hehlgans T; Leibniz Institute of Immunotherapy (LIT), Chair for Immunology, University of Regensburg, 93053 Regensburg, Germany., Pfeffer K; Institute of Medical, Microbiology and Hospital Hygiene, University Hospital Düsseldorf, 40225 Düsseldorf, Germany., Crosti M; INGM, Istituto Nazionale di Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Abrignani S; INGM, Istituto Nazionale di Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy; Department of Clinical Science and Community Health (DISCCO), University of Milan, Milan, Italy., Evans SM; Skaggs School of Pharmacy, University of California at San Diego, La Jolla, CA 92093, USA., Sitia G; Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy., Guimarães-Camboa N; Institute of Cardiovascular Regeneration, Goethe-University, Frankfurt 60590, Germany; German Center for Cardiovascular Research, Berlin (partner site Frankfurt Rhine-Main), Germany., Russo V; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., van de Pavert SA; Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, INSERM, CNRS, Marseille, France., Garcia-Manteiga JM; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Brendolan A; Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: brendolan.andrea@hsr.it.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2022 Apr 12; Vol. 55 (4), pp. 606-622.e6. Date of Electronic Publication: 2022 Mar 30.
DOI: 10.1016/j.immuni.2022.03.002
Abstrakt: 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.
Competing Interests: Declaration of interests The authors declare no competing interests.
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Databáze: MEDLINE