TY - JOUR
T1 - Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation
AU - Kenswil, Keane Jared Guillaume
AU - Pisterzi, Paola
AU - Sanchez-Duffhues, Gonzalo
AU - van Dijk, Claire
AU - Lolli, Andrea
AU - Knuth, Callie
AU - Vanchin, Byambasuren
AU - Jaramillo, Adrian Christopher
AU - Hoogenboezem, Remco Michiel
AU - Sanders, Mathijs Arnoud
AU - Feyen, Jacqueline
AU - Cupedo, Tom
AU - Costa, Ivan G.
AU - Li, Ronghui
AU - Bindels, Eric Monique Johannes
AU - Lodder, Kirsten
AU - Blom, Bianca
AU - Bos, Pieter Koen
AU - Goumans, Marie-Jose
AU - ten Dijke, Peter
AU - Farrell, Eric
AU - Krenning, Guido
AU - Raaijmakers, Marc Hermanus Gerardus Petrus
N1 - Copyright © 2021 Elsevier Inc. All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.stem.2021.01.006
DO - 10.1016/j.stem.2021.01.006
M3 - Article
C2 - 33561425
SN - 1934-5909
VL - 28
SP - 653-670.e11
JO - Cell stem cell
JF - Cell stem cell
IS - 4
ER -