Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance

Jingjing Cao; Lingling Zhang; Yong Wan; Hanjun Li; Rujiang Zhou; Heyuan Ding; Yongzhong Liu; Zhengju Yao; Xizhi Guo

doi:10.1002/eji.201445405

Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance

Eur J Immunol. 2015 Sep;45(9):2650-60. doi: 10.1002/eji.201445405. Epub 2015 Aug 21.

Authors

Jingjing Cao¹, Lingling Zhang¹, Yong Wan¹, Hanjun Li¹, Rujiang Zhou¹, Heyuan Ding², Yongzhong Liu³, Zhengju Yao¹, Xizhi Guo¹

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
² The Fifth People's Hospital of Shanghai, Fudan University, China.
³ Shanghai Cancer Institute, Shanghai, China.

PMID: 26173091
DOI: 10.1002/eji.201445405

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.

Keywords: B cell; HSC maintenance; Osteoblast; T-cell infiltration; Wntless.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes / immunology*
B-Lymphocytes / pathology
Bone Marrow Cells / cytology
Bone Marrow Cells / immunology
Bone and Bones / cytology
Bone and Bones / immunology
Cell Differentiation
Cell Movement
Gene Expression Regulation
Hematopoiesis / genetics*
Hematopoiesis / immunology
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / immunology
Intracellular Signaling Peptides and Proteins / deficiency
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / immunology
Lymphopoiesis / genetics*
Lymphopoiesis / immunology
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / immunology
Mice
Mice, Knockout
Nestin / genetics
Nestin / immunology
Osteoblasts / cytology
Osteoblasts / immunology
Paracrine Communication / genetics
Paracrine Communication / immunology
Receptors, G-Protein-Coupled / deficiency
Receptors, G-Protein-Coupled / genetics*
Receptors, G-Protein-Coupled / immunology
Stem Cell Niche / genetics
Stem Cell Niche / immunology*
T-Lymphocytes / immunology*
T-Lymphocytes / pathology
Wnt Signaling Pathway*

Substances

Gpr177 protein, mouse
Intracellular Signaling Peptides and Proteins
Nes protein, mouse
Nestin
Receptors, G-Protein-Coupled