학술논문

Distinct skeletal stem cell types orchestrate long bone skeletogenesis
Document Type
article
Source
Subject
Medical Biotechnology
Biomedical and Clinical Sciences
Transplantation
Stem Cell Research
Stem Cell Research - Nonembryonic - Human
Regenerative Medicine
Stem Cell Research - Nonembryonic - Non-Human
Underpinning research
1.1 Normal biological development and functioning
Musculoskeletal
Adipose Tissue
Animals
Bone Development
Bone Marrow
Bone Marrow Cells
Bone and Bones
Gene Expression Regulation
Developmental
Hematopoietic Stem Cells
Male
Mice
Mice
Inbred C57BL
Pericytes
Stem Cell Niche
Stromal Cells
Transcriptome
bone
diversity
mesenchymal stromal cells
mouse
regenerative medicine
skeletal stem cells
stem cells
Biochemistry and Cell Biology
Biological sciences
Biomedical and clinical sciences
Health sciences
Language
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.