title: Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow.
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.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, P.R. China.|Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.|Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.|Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University 56 Lingyuanxi Road, Guangzhou 510055, China.
authors.forename: Lusai
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.|Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University 56 Lingyuanxi Road, Guangzhou 510055, China.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, College of Physician and Surgeons Columbia University Medical Center, 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hei
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Chotkowski
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University Medical Center 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Tarnow
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Finkel
authors.affiliation: Departments of Microbiology &Immunology and Rehabilitation &Regenerative Medicine 630 W. 168 St., New York, NY 10032, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, P.R. China.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR) 630 W. 168 St., New York, NY 10032, USA.|Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University 56 Lingyuanxi Road, Guangzhou 510055, China.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009432:Neural Crest / Q000166:cytology; D055153:Stem Cell Niche; D059467:Transcriptome
chemical_list: D015703:Antigens, CD