Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation

Keane Jared Guillaume Kenswil, Paola Pisterzi, Gonzalo Sánchez-Duffhues, Claire van Dijk, Andrea Lolli, Callie Knuth, Byambasuren Vanchin, Adrian Christopher Jaramillo, Remco Michiel Hoogenboezem, Mathijs Arnoud Sanders, Jacqueline Feyen, Tom Cupedo, Ivan G. Costa, Ronghui Li, Eric Moniqué Johannes Bindels, Kirsten Lodder, Bianca Blom, Pieter Koen Bos, Marie José Goumans, Peter ten DijkeEric Farrell, Guido Krenning, Marc Hermanus Gerardus Petrus Raaijmakers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)
40 Downloads (Pure)

Abstract

Bone marrow stromal cells (BMSCs) play pivotal roles in tissue maintenance and regeneration. Their origins, however, remain incompletely understood. Here we identify rare LNGFR+ cells in human fetal and regenerative bone marrow that co-express endothelial and stromal markers. This endothelial subpopulation displays transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT) and can generate multipotent stromal cells that reconstitute the bone marrow (BM) niche upon transplantation. Single-cell transcriptomics and lineage tracing in mice confirm robust and sustained contributions of EndoMT to bone precursor and hematopoietic niche pools. Interleukin-33 (IL-33) is overexpressed in subsets of EndoMT cells and drives this conversion process through ST2 receptor signaling. These data reveal generation of tissue-forming BMSCs from mouse and human endothelial cells and may be instructive for approaches to human tissue regeneration.

Original languageEnglish
Pages (from-to)653-670.e11
JournalCell Stem Cell
Volume28
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021

Bibliographical note

Acknowledgments
We would like to thank Dr. Kirsten van Lom, Dr. Eric Braakman, Lucia Duinhouwer, and Mariëtte ter Borg for providing CD34+ cells and help with human BM sampling; Natalie Papazian for helping to process fetal tissue; Dr. Elwin Rombouts, Peter van Geel, and Michael Vermeulen for operating the BD FACSARIA III; Maria Mylona, Maria Adisty, and Paulette van Strien for performing FACs and RNA-seq; Onno Roovers, Almira Henić, Eline Pronk, Gert-Jan Kremers, Bella Banjanin, Ursula Stalmann, Nils Bayer, and Madelon de Jong for providing technical advice and assistance; Esther Siteur-van Rijnstra and Cynthia van der Linden for providing technical assistance with fetal tissue; Mathias Francois and lab members for help with the lineage tracing experiments; Emma de Pater for advice concerning mouse breeding; members of the Erasmus MC Department of Hematology for scientific discussions; and Egied Simons for assisting with illustrations. This work was supported by an Erasmus MC fellowship award (to M.H.G.P.R.). M.-J.G. and G.S.-D. are supported by the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation , Dutch Federation of University Medical Centers , Netherlands Organization for Health Research and Development , and the Royal Netherlands Academy of Sciences (grant CVON 2014-11 RECONNECT). G.S.-D. is also sponsored by a trampoline grant (# 22379 ) from AFM-Telethon and FOP Italia (Grant Italia 2020 ). A.L. is supported by the European Union Horizon 2020 Research and Innovation Program under grant agreement 801159 .

Publisher Copyright: © 2021 Elsevier Inc.

Fingerprint

Dive into the research topics of 'Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation'. Together they form a unique fingerprint.

Cite this