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

Keane Jared Guillaume Kenswil, Paola Pisterzi, Gonzalo Sanchez-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 Monique Johannes Bindels, Kirsten Lodder, Bianca Blom, Pieter Koen Bos, Marie-Jose Goumans, Peter ten DijkeEric Farrell, Guido Krenning, Marc Hermanus Gerardus Petrus Raaijmakers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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
Number of pages29
JournalCell stem cell
Volume28
Issue number4
Early online date1-Feb-2021
DOIs
Publication statusPublished - 1-Apr-2021

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