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.
Highlights
Bone marrow stromal cells (BMSCs) contain a subset of putative adult stem cells that emerge during development and have a tissue-restricted, multilineage differentiation capacity (Bianco et al, 2008; Dominici et al, 2006)
Identification of rare LNGFR-expressing human Endothelial cells (ECs) in regenerative and fetal bone marrow (BM) We recently characterized a distinct subset of CD105+ ECs emerging during human fetal development and BM regeneration after injury (Kenswil et al, 2018)
Interrogation of the transcriptome of these ECs revealed expression of transcripts typically associated with stromal cell fates, including THY1 (CD90) and NGFR (CD271) (Table S1), suggesting the possibility that a subset of hRECs with stromal properties might exist during human fetal development
Summary
Keane Jared Guillaume Kenswil, Paola Pisterzi, Gonzalo Sanchez-Duffhues, ..., Eric Farrell, Guido Krenning, Marc Hermanus Gerardus Petrus Raaijmakers. Endothelial cells (ECs) may contribute to tissue development and regeneration. Kenswil et al reveal a process of transition of ECs to bone marrow stromal cells (BMSCs), contributing to bone marrow and niche formation in mammals. IL-33 is identified as a driver of this process.
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