title: Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance.
abstract: Osteoblasts and perivascular stromal cells constitute essential niches for HSC self-renewal and maintenance in the bone marrow. Wnt signaling is important to maintain HSC integrity. However, the paracrine role of Wnt proteins in osteoblasts-supported HSC maintenance and differentiation remains unclear. Here, we investigated hematopoiesis in mice with Wntless (Wls) deficiency in osteoblasts or Nestin-positive mesenchymal progenitor cells, which presumptively block Wnt secretion in osteoblasts. We detected defective B-cell lymphopoiesis and abnormal T-cell infiltration in the bone marrow of Wls mutant mice. Notably, no impact on HSC frequency and repopulation in the bone marrow was observed with the loss of osteoblastic Wls. Our findings revealed a supportive role of Wnts in osteoblasts-regulated B-cell lymphopoiesis. They also suggest a preferential niche role of osteoblastic Wnts for lymphoid cells rather than HSCs, providing new clues for the molecular nature of distinct niches occupied by different hematopoietic cells.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hanjun
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Rujiang
authors.initials: R
authors.lastname: Zhou
authors.affiliation: The Fifth People's Hospital of Shanghai, Fudan University, China.
authors.forename: Heyuan
authors.initials: H
authors.lastname: Ding
authors.affiliation: Shanghai Cancer Institute, Shanghai, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D001842:Bone and Bones / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics* / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D064231:Nestin / Q000235:genetics / Q000276:immunology; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology; D019899:Paracrine Communication / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D055153:Stem Cell Niche / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D060449:Wnt Signaling Pathway
chemical_list: C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C577485:Nes protein, mouse; D064231:Nestin; D043562:Receptors, G-Protein-Coupled
keywords: B cell; HSC maintenance; Osteoblast; T-cell infiltration; Wntless