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1.
Elife ; 102021 07 19.
Article in English | MEDLINE | ID: mdl-34280086

ABSTRACT

Skeletal stem and progenitor cell populations are crucial for bone physiology. Characterization of these cell types remains restricted to heterogenous bulk populations with limited information on whether they are unique or overlap with previously characterized cell types. Here we show, through comprehensive functional and single-cell transcriptomic analyses, that postnatal long bones of mice contain at least two types of bone progenitors with bona fide skeletal stem cell (SSC) characteristics. An early osteochondral SSC (ocSSC) facilitates long bone growth and repair, while a second type, a perivascular SSC (pvSSC), co-emerges with long bone marrow and contributes to shape the hematopoietic stem cell niche and regenerative demand. We establish that pvSSCs, but not ocSSCs, are the origin of bone marrow adipose tissue. Lastly, we also provide insight into residual SSC heterogeneity as well as potential crosstalk between the two spatially distinct cell populations. These findings comprehensively address previously unappreciated shortcomings of SSC research.


Subject(s)
Bone Development , Bone and Bones/metabolism , Stromal Cells/metabolism , Adipose Tissue , Animals , Bone Marrow , Bone Marrow Cells , Gene Expression Regulation, Developmental , Hematopoietic Stem Cells/metabolism , Male , Mice , Mice, Inbred C57BL , Pericytes , Stem Cell Niche , Transcriptome
2.
JBMR Plus ; 4(10): e10398, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33103027

ABSTRACT

Delayed union or nonunion are relatively rare complications after fracture surgery, but when they do occur, they can result in substantial morbidity for the patient. In many cases, the etiology of impaired fracture healing is uncertain and attempts to determine the molecular basis for delayed union and nonunion formation have been limited. Prospectively isolating skeletal stem cells (SSCs) from fracture tissue samples at the time of surgical intervention represent a feasible methodology to determine a patient's biologic risk for compromised fracture healing. This report details a case in which functional in vitro readouts of SSCs derived from human fracture tissue at time of injury predicted a poor fracture healing outcome. This case suggests that it may be feasible to stratify a patient's fracture healing capacity and predict compromised fracture healing by prospectively isolating and analyzing SSCs during the index fracture surgery. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

3.
Elife ; 52016 12 13.
Article in English | MEDLINE | ID: mdl-27960074

ABSTRACT

The discovery that proteins called c-type lectins promote bone growth could lead to new treatments for age-related bone disorders.


Subject(s)
Lectins , Osteogenesis , Adult , Bone Development , Bone and Bones , Humans , Intercellular Signaling Peptides and Proteins
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