Concise Review: Conceptualizing Paralogous Stem‐Cell Niches and Unfolding Bone Marrow Progenitor Cell Identities

• Published in: Stem cells (Dayton, Ohio) Ohio), 2018-01, Vol.36 (1), p.11-21
• Main Authors: Chen, Kevin G., Johnson, Kory R., McKay, Ronald D.G., Robey, Pamela G.
• Format: Article
• Language: English
• Subjects: Adult stem cells; Animal models; Bone marrow; Bone Marrow - metabolism; Cell Differentiation; Cell Lineage; Developmental stages; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Humans; In vivo tracking; Leptin receptors; Life span; Marrow stromal cells; Mesenchymal stem cells; Mesenchyme; Nestin; Niches; Osteoblast; Pericytes; Progenitor cells; Receptors; Regeneration (physiology); Regenerative medicine; Stem Cell Niche - genetics; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Stromal cells; Tissue engineering; Transcription
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2711

Lineage commitment and differentiation of skeletal stem cells/bone marrow stromal cells (SSCs/BMSCs, often called bone marrow‐derived “mesenchymal stem/stromal” cells) offer an important opportunity to study skeletal and hematopoietic diseases, and for tissue engineering and regenerative medicine. Currently, many studies in this field have relied on cell lineage tracing methods in mouse models, which have provided a significant advancement in our knowledge of skeletal and hematopoietic stem‐cell niches in bone marrow (BM). However, there is a lack of agreement in numerous fundamental areas, including origins of various BM stem‐cell niches, cell identities, and their physiological roles in the BM. In order to resolve these issues, we propose a new hypothesis of “paralogous” stem‐cell niches (PSNs); that is, progressively altered parallel niches within an individual species throughout the life span of the organism. A putative PSN code seems to be plausible based on analysis of transcriptional signatures in two representative genes that encode Nes‐GFP and leptin receptors, which are frequently used to monitor SSC lineage development in BM. Furthermore, we suggest a dynamic paralogous BM niche (PBMN) model that elucidates the coupling and uncoupling mechanisms between BM stem‐cell niches and their zones of active regeneration during different developmental stages. Elucidation of these PBMNs would enable us to resolve the existing controversies, thus paving the way to achieving precision regenerative medicine and pharmaceutical applications based on these BM cell resources. Stem Cells 2018;36:11–21 Top panel depicts “paralogous” bone marrow stem‐cell niches (PBMNs), such as perivascular and endosteal surface niches for skeletal stem cells and hematopoietic stem cells. These PBMNs are progressively altered, parallel niches of bone marrow at different developmental stages of bone marrow. A proposed dynamic Yin‐Yang niche between the periarteriolar and perisinusoidal interface (i.e., the AS interface) might underlie the coupling and uncoupling of PBMNs with their regenerative zones. Lower panel illustrates alterations of PBMNs based on analysis of transcriptional activities in three representative transgene reporters (i.e., Nes‐Cre, Nes‐GFP, and Lepr‐Cre) that are associated with the genes encoding nestin (Nes) and leptin receptors (Lepr). In vivo cell‐fate mapping at various PBMNs would aid in resolving existing controversies on bone marrow stem‐cell origins and