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Origin and Differentiation Trajectories of Fibroblastic Reticular Cells in the Splenic White Pulp

43 Pages Posted: 17 Aug 2018 Sneak Peek Status: Review Complete

See all articles by Hung-Wei Cheng

Hung-Wei Cheng

Kantonsspital St. Gallen - Institute of Immunobiology

Lucas Onder

Kantonsspital St. Gallen - Institute of Immunobiology

Mario Novkovic

Kantonsspital St. Gallen - Institute of Immunobiology

Charlotte Soneson

University of Zurich - Institute of Molecular Life Sciences

Mechthild Lütge

Kantonsspital St. Gallen - Institute of Immunobiology

Natalia Pikor

Kantonsspital St. Gallen - Institute of Immunobiology

Elke Scandella

Kantonsspital St. Gallen - Institute of Immunobiology

Mark D. Robinson

University of Zurich - Institute of Molecular Life Sciences

Jun-ichi Miyazaki

Osaka University - Division of Stem Cell Regulation Research

Thomas Rülicke

University of Veterinary Medicine, Vienna - Institute of Laboratory Animal Science

Thomas Hehlgans

University of Regensburg - University Medical Center of Regensburg

Burkhard Ludewig

Kantonsspital St. Gallen - Institute of Immunobiology

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Abstract

The splenic white pulp is underpinned by poorly characterized stromal cells that demarcate distinct immune cell microenvironments. Here, definition of the embryonic origin and tracing of the differentiation trajectories of fibroblastic reticular cells (FRCs) was enabled by the establishment of FRC-specific fate-mapping in mice. We found that all reticular cell subsets descend from pluripotent progenitors that emerge at embryonic day 19.5 from Sca-1 periarterial progenitors. Commitment of FRC progenitors was concluded during the first week of postnatal life through occupation of niches along developing central arterioles. Single cell transcriptomic analysis facilitated deconvolution of FRC differentiation trajectories and indicated that perivascular reticular cells function both as adult lymphoid organizer cells and mural cell progenitors. Finally, the lymphotoxin-β receptor-independent sustenance of postnatal progenitor stemness unveiled that systemic immune surveillance in the splenic white pulp is governed through subset specification of reticular cells from a pluripotent periarterial progenitor cell.

Suggested Citation

Cheng, Hung-Wei and Onder, Lucas and Novkovic, Mario and Soneson, Charlotte and Lütge, Mechthild and Pikor, Natalia and Scandella, Elke and Robinson, Mark D. and Miyazaki, Jun-ichi and Rülicke, Thomas and Hehlgans, Thomas and Ludewig, Burkhard, Origin and Differentiation Trajectories of Fibroblastic Reticular Cells in the Splenic White Pulp (2018). Available at SSRN: https://ssrn.com/abstract=3232167 or http://dx.doi.org/10.2139/ssrn.3232167
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Hung-Wei Cheng

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Lucas Onder

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Mario Novkovic

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Charlotte Soneson

University of Zurich - Institute of Molecular Life Sciences

Winterthurerstrasse 190
Zurich, CH-8057
Switzerland

Mechthild Lütge

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Natalia Pikor

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Elke Scandella

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Mark D. Robinson

University of Zurich - Institute of Molecular Life Sciences ( email )

Winterthurerstrasse 190
Zurich, CH-8057
Switzerland

Jun-ichi Miyazaki

Osaka University - Division of Stem Cell Regulation Research

Osaka
Japan

Thomas Rülicke

University of Veterinary Medicine, Vienna - Institute of Laboratory Animal Science

Veterinärpl. 1
1210 Wien
Austria

Thomas Hehlgans

University of Regensburg - University Medical Center of Regensburg

93040 Regensburg
D-93040 Regensburg, 93053
Germany

Burkhard Ludewig (Contact Author)

Kantonsspital St. Gallen - Institute of Immunobiology ( email )

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

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