PMID- 29563184 OWN - NLM STAT- MEDLINE DCOM- 20180626 LR - 20181202 IS - 1549-5477 (Electronic) IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 32 IP - 5-6 DP - 2018 Mar 1 TI - Stem cell niche-specific Ebf3 maintains the bone marrow cavity. PG - 359-372 LID - 10.1101/gad.311068.117 [doi] AB - Bone marrow is the tissue filling the space between bone surfaces. Hematopoietic stem cells (HSCs) are maintained by special microenvironments known as niches within bone marrow cavities. Mesenchymal cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-positive (LepR(+)) cells, are a major cellular component of HSC niches that gives rise to osteoblasts in bone marrow. However, it remains unclear how osteogenesis is prevented in most CAR/LepR(+) cells to maintain HSC niches and marrow cavities. Here, using lineage tracing, we found that the transcription factor early B-cell factor 3 (Ebf3) is preferentially expressed in CAR/LepR(+) cells and that Ebf3-expressing cells are self-renewing mesenchymal stem cells in adult marrow. When Ebf3 is deleted in CAR/LepR(+) cells, HSC niche function is severely impaired, and bone marrow is osteosclerotic with increased bone in aged mice. In mice lacking Ebf1 and Ebf3, CAR/LepR(+) cells exhibiting a normal morphology are abundantly present, but their niche function is markedly impaired with depleted HSCs in infant marrow. Subsequently, the mutants become progressively more osteosclerotic, leading to the complete occlusion of marrow cavities in early adulthood. CAR/LepR(+) cells differentiate into bone-producing cells with reduced HSC niche factor expression in the absence of Ebf1/Ebf3 Thus, HSC cellular niches express Ebf3 that is required to create HSC niches, to inhibit their osteoblast differentiation, and to maintain spaces for HSCs. CI - (c) 2018 Seike et al.; Published by Cold Spring Harbor Laboratory Press. FAU - Seike, Masanari AU - Seike M AD - Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Immunology Frontier Research Center, World Premier International Research Center (WPI), Osaka University, Osaka 565-0871, Japan. FAU - Omatsu, Yoshiki AU - Omatsu Y AD - Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Immunology Frontier Research Center, World Premier International Research Center (WPI), Osaka University, Osaka 565-0871, Japan. FAU - Watanabe, Hitomi AU - Watanabe H AD - Laboratory of Integrative Biological Science and Animal Experiments for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. FAU - Kondoh, Gen AU - Kondoh G AD - Laboratory of Integrative Biological Science and Animal Experiments for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. FAU - Nagasawa, Takashi AU - Nagasawa T AD - Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Immunology Frontier Research Center, World Premier International Research Center (WPI), Osaka University, Osaka 565-0871, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180321 PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Ebf1 protein, mouse) RN - 0 (Ebf3 protein, mouse) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) SB - IM CIN - Genes Dev. 2018 Mar 1;32(5-6):324-326. PMID: 29593065 MH - Age Factors MH - Animals MH - Bone Marrow/*metabolism/pathology MH - Cell Differentiation MH - Cell Lineage MH - Gene Expression Regulation MH - Mesenchymal Stem Cells/cytology/*metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Osteogenesis/genetics MH - Stem Cell Niche MH - Trans-Activators/genetics/metabolism MH - Transcription Factors/genetics/*metabolism PMC - PMC5900710 OTO - NOTNLM OT - Ebf3 OT - bone OT - hematopoietic stem cell OT - mesenchymal stem cell OT - stem cell niche EDAT- 2018/03/23 06:00 MHDA- 2018/06/27 06:00 PMCR- 2018/09/01 CRDT- 2018/03/23 06:00 PHST- 2017/12/22 00:00 [received] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/03/23 06:00 [pubmed] PHST- 2018/06/27 06:00 [medline] PHST- 2018/03/23 06:00 [entrez] PHST- 2018/09/01 00:00 [pmc-release] AID - gad.311068.117 [pii] AID - 10.1101/gad.311068.117 [doi] PST - ppublish SO - Genes Dev. 2018 Mar 1;32(5-6):359-372. doi: 10.1101/gad.311068.117. Epub 2018 Mar 21.