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. 2021:434:1-31.
doi: 10.1007/978-3-030-86016-5_1.

Skeletal Stem Cells as the Developmental Origin of Cellular Niches for Hematopoietic Stem and Progenitor Cells

Thomas H Ambrosi  1   2 , Charles K F Chan  3   4
Affiliations

Skeletal Stem Cells as the Developmental Origin of Cellular Niches for Hematopoietic Stem and Progenitor Cells

Thomas H Ambrosi et al. Curr Top Microbiol Immunol. 2021.

Abstract

The skeletal system is a highly complex network of mesenchymal, hematopoietic, and vasculogenic stem cell lineages that coordinate the development and maintenance of defined microenvironments, so-called niches. Technological advancements in recent years have allowed for the dissection of crucial cell types as well as their autocrine and paracrine signals that regulate these niches during development, homeostasis, regeneration, and disease. Ingress of blood vessels and bone marrow hematopoiesis are initiated by skeletal stem cells (SSCs) and their more committed downstream lineage cell types that direct shape and form of skeletal elements. In this chapter, we focus on the role of SSCs as the developmental origin of niches for hematopoietic stem and progenitor cells. We discuss latest updates in the definition of SSCs, cellular processes establishing and maintaining niches, as well as alterations of stem cell microenvironments promoting malignancies. We conclude with an outlook on future studies that could take advantage of SSC-niche engineering as a basis for the development of new therapeutic tools to not only treat bone-related diseases but also maladies stemming from derailed niche dynamics altering hematopoietic output.

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Figures

Fig. 1
Fig. 1. Multiple Skeletal Stem Cell (SSC) Subtypes.
SSCs of long bones are found in specific anatomical localizations. Their microenvironment determines lineage contributions and functions
Fig. 2
Fig. 2. The hematopoietic stem cell niche in homeostasis and disease/aging.
Left, homeostatic HSC niche showing HSCs in proximity to blood vessels surrounded by key cell types that secrete regulatory factors. Right, aging and disease alters cellular composition of HSC niches leading to higher HSC prevalence and altered lineage output. HSC aging can lead to niche changes or cellular changes in the microenvironment can lead to HSC aging
See this image and copyright information in PMC

References

    1. Acar M, Kocherlakota KS, Murphy MM et al. (2015) Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature 526:126–130. 10.1038/nature15250 - DOI - PMC - PubMed
    1. Agarwal A, Morrone K, Bartenstein M et al. (2016) Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell Investig 3. 10.3978/j.issn.2306-9759.2016.02.03 - DOI - PMC - PubMed
    1. Agarwal R, Dvorak CC, Prohaska S et al. (2019) Toxicity-free hematopoietic stem cell engraftment achieved with anti-CD117 monoclonal antibody conditioning. Biol Blood Marrow Transplant 25:S92. 10.1016/j.bbmt.2018.12.172 - DOI
    1. Ambrosi TH, Goodnough LH, Steininger HM et al. (2020) Geriatric fragility fractures are associated with a human skeletal stem cell defect. Aging Cell 19:e13164. 10.1111/acel.13164 - DOI - PMC - PubMed
    1. Ambrosi TH, Longaker MT, Chan CKF (2019) A revised perspective of skeletal stem cell biology. Front Cell Dev Biol 7:189. 10.3389/fcell.2019.00189 - DOI - PMC - PubMed