Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow.

Nan Jiang,Guodong Yang,Jeremy J Mao,Ling He,Dennis P Tarnow,Gregory Chotkowski,Myron Finkel,Lusai Xiang,Yanheng Zhou,Mo Chen,Lei Ding,Thomas K Hei

doi:10.1038/srep36411

Abstract

Hematopoietic stem cells (HSCs) in the endosteum of mesoderm-derived appendicular bones have been extensively studied. Neural crest-derived bones differ from appendicular bones in developmental origin, mode of bone formation and pathological bone resorption. Whether neural crest-derived bones harbor HSCs is elusive. Here, we discovered HSC-like cells in postnatal murine mandible, and benchmarked them with donor-matched, mesoderm-derived femur/tibia HSCs, including clonogenic assay and long-term culture. Mandibular CD34 negative, LSK cells proliferated similarly to appendicular HSCs, and differentiated into all hematopoietic lineages. Mandibular HSCs showed a consistent deficiency in lymphoid differentiation, including significantly fewer CD229 + fractions, PreProB, ProB, PreB and B220 + slgM cells. Remarkably, mandibular HSCs reconstituted irradiated hematopoietic bone marrow in vivo, just as appendicular HSCs. Genomic profiling of osteoblasts from mandibular and femur/tibia bone marrow revealed deficiencies in several HSC niche regulators among mandibular osteoblasts including Cxcl12. Neural crest derived bone harbors HSCs that function similarly to appendicular HSCs but are deficient in the lymphoid lineage. Thus, lymphoid deficiency of mandibular HSCs may be accounted by putative niche regulating genes. HSCs in craniofacial bones have functional implications in homeostasis, osteoclastogenesis, immune functions, tumor metastasis and infections such as osteonecrosis of the jaw.

Highlights

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiate into all blood lineages
HSCs interact with various niche cells in bone marrow including perivascular stromal cells, mesenchymal stromal cells, endothelial cells, osteoblasts, macrophage, adipocytes and sympathetic neurons in ways that require further understanding[19,20,21]
Mandibular CD34ˉLSK cells differentiated into colony-forming unit erythroid (CFU-E), mature burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte/ macrophage (CFU-GM), CFU-granulocyte/ erythroid/megakaryocyte/macrophage (CFU-GEMM) and pre-B lymphoid (CFU-Pre B) progenitors (Fig. 1E)

Summary

Introduction

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiate into all blood lineages. Conditional deletion of Cxcl[12] from perivascular stromal cells affected HSCs proliferation, self-renew and trafficking and depleted certain restricted progenitors[17]. HSCs interact with various niche cells in bone marrow including perivascular stromal cells, mesenchymal stromal cells, endothelial cells, osteoblasts, macrophage, adipocytes and sympathetic neurons in ways that require further understanding[19,20,21]. Compared to iliac crest bone marrow stromal cells, facial bones including the maxilla and mandible have rich vasculature, with bone marrow stromal cells proliferating at more rapid rates, and formed more ectopic bone in vivo[24], suggesting that neural crest-derived stromal cells in facial bones may preserve different stromal microenvironment for putative HSCs. In this study, we identified hematopoietic stem cells in the mandible and benchmarked mandibular HSCs with donor-matched appendicular HSCs isolated from donor-matched femur/ tibia

Methods

Results

Conclusion