PMID- 33561425 OWN - NLM STAT- MEDLINE DCOM- 20210519 LR - 20210519 IS - 1875-9777 (Electronic) IS - 1875-9777 (Linking) VI - 28 IP - 4 DP - 2021 Apr 1 TI - Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation. PG - 653-670.e11 LID - S1934-5909(21)00006-0 [pii] LID - 10.1016/j.stem.2021.01.006 [doi] 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Kenswil, Keane Jared Guillaume AU - Kenswil KJG AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Pisterzi, Paola AU - Pisterzi P AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Sanchez-Duffhues, Gonzalo AU - Sanchez-Duffhues G AD - Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden 2300 RC, the Netherlands. FAU - van Dijk, Claire AU - van Dijk C AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Lolli, Andrea AU - Lolli A AD - Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 DR, the Netherlands. FAU - Knuth, Callie AU - Knuth C AD - Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 DR, the Netherlands. FAU - Vanchin, Byambasuren AU - Vanchin B AD - Cardiovascular Regenerative Medicine Research Group, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands. FAU - Jaramillo, Adrian Christopher AU - Jaramillo AC AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Hoogenboezem, Remco Michiel AU - Hoogenboezem RM AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Sanders, Mathijs Arnoud AU - Sanders MA AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Feyen, Jacqueline AU - Feyen J AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Cupedo, Tom AU - Cupedo T AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Costa, Ivan G AU - Costa IG AD - Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen, Aachen 52074, Germany. FAU - Li, Ronghui AU - Li R AD - Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen, Aachen 52074, Germany. FAU - Bindels, Eric Monique Johannes AU - Bindels EMJ AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. FAU - Lodder, Kirsten AU - Lodder K AD - Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden 2300 RC, the Netherlands. FAU - Blom, Bianca AU - Blom B AD - Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam institute for Infection & Immunity, Amsterdam 1105 AZ, the Netherlands. FAU - Bos, Pieter Koen AU - Bos PK AD - Department of Orthopaedics, Erasmus MC, Rotterdam 3015CE, the Netherlands. FAU - Goumans, Marie-Jose AU - Goumans MJ AD - Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden 2300 RC, the Netherlands. FAU - Ten Dijke, Peter AU - Ten Dijke P AD - Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden 2300 RC, the Netherlands; Oncode Institute, Leiden University Medical Centre, Leiden 2300 RC, the Netherlands. FAU - Farrell, Eric AU - Farrell E AD - Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 DR, the Netherlands. FAU - Krenning, Guido AU - Krenning G AD - Cardiovascular Regenerative Medicine Research Group, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands. FAU - Raaijmakers, Marc Hermanus Gerardus Petrus AU - Raaijmakers MHGP AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015 CN, the Netherlands. Electronic address: m.h.g.raaijmakers@erasmusmc.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210208 PL - United States TA - Cell Stem Cell JT - Cell stem cell JID - 101311472 SB - IM MH - Animals MH - *Bone Marrow MH - Bone Marrow Cells MH - Endothelial Cells MH - Endothelium MH - *Hematopoietic Stem Cell Transplantation MH - Hematopoietic Stem Cells MH - Mice MH - Stromal Cells OTO - NOTNLM OT - EndoMT OT - development OT - endothelial OT - endothelial-mesenchymal transition OT - hematopoietic stem cell OT - mesenchymal OT - niche OT - regeneration OT - stroma OT - transdifferentiation COIS- Declaration of interests The authors declare no competing interests. EDAT- 2021/02/10 06:00 MHDA- 2021/05/20 06:00 CRDT- 2021/02/09 20:09 PHST- 2020/03/20 00:00 [received] PHST- 2020/09/29 00:00 [revised] PHST- 2021/01/11 00:00 [accepted] PHST- 2021/02/10 06:00 [pubmed] PHST- 2021/05/20 06:00 [medline] PHST- 2021/02/09 20:09 [entrez] AID - S1934-5909(21)00006-0 [pii] AID - 10.1016/j.stem.2021.01.006 [doi] PST - ppublish SO - Cell Stem Cell. 2021 Apr 1;28(4):653-670.e11. doi: 10.1016/j.stem.2021.01.006. Epub 2021 Feb 8.