Regional specialization and fate specification of bone stromal cells in skeletal development

Sivaraj, Kishor K.; Jeong, Hyun‐Woo; Dharmalingam, Backialakshmi; Zeuschner, Dagmar; Adams, Susanne; Potente, Michael; Adams, Ralf H.

doi:10.1016/j.celrep.2021.109352

Cited by 64 publications

(65 citation statements)

References 67 publications

(96 reference statements)

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“…The same study has also proposed that septoclasts emerge from pericytes. However, scRNA-seq studies have so far failed to identify a distinct pericyte population in developing and adult bone 33 – 35 , whereas the sum of our findings, including genetic fate tracking experiments, supports that septoclasts have a non-hematopoietic origin and are derived from mpMSCs. This conclusion is also consistent with our previous characterization of Pdgfrb-CreERT2 -expressing cells in developing bone, which showed that the transgene initially labels mesenchymal stromal cells in the metaphysis, which later give rise to other mesenchymal cell populations including reticular cells in marrow and adipocytes 35 .…”

Section: Discussionmentioning

confidence: 49%

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Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing

et al. 2022

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Developmental osteogenesis, physiological bone remodelling and fracture healing require removal of matrix and cellular debris. Osteoclasts generated by the fusion of circulating monocytes degrade bone, whereas the identity of the cells responsible for cartilage resorption is a long-standing and controversial question. Here we show that matrix degradation and chondrocyte phagocytosis are mediated by fatty acid binding protein 5-expressing cells representing septoclasts, which have a mesenchymal origin and are not derived from haematopoietic cells. The Notch ligand Delta-like 4, provided by endothelial cells, is necessary for septoclast specification and developmental bone growth. Consistent with the termination of growth, septoclasts disappear in adult and ageing bone, but re-emerge in association with growing vessels during fracture healing. We propose that cartilage degradation is mediated by rare, specialized cells distinct from osteoclasts. Our findings have implications for fracture healing, which is frequently impaired in aging humans.

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Section: Discussionmentioning

confidence: 49%

“…Pdgfrb(BAC)Cre-ERT2 (ref. 35 ) or Vav1-Cre 37 transgenic mice were interbred with Gt(Rosa26) ACTB-tdTomato-EGFP reporter animals 19 for cell fate tracking. Chondrocytes were targeted using Acan-CreERT2 (ref.…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing

et al. 2022

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“…34 In addition, the heterogeneity of MSCs is related to the location of their origin. 35 , 36 MSCs in different mouse molars contain different concentrations of key tooth development signaling molecules, i.e., bone morphogenetic proteins (BMPs), or respond differently to sonic hedgehog (Shh). These differences, in turn, lead to varying MSCs behaviors, eventually resulting in teeth with different crown morphologies and root numbers.…”

Section: Discussionmentioning

confidence: 99%

Tracing PRX1+ cells during molar formation and periodontal ligament reconstruction

Gong

Zhang

et al. 2022

Int J Oral Sci

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Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1+ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1+ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1+ cells in PDL cells. The behavior of PRX1+ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1+ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1+ cells; during transplanted teeth PDL reconstruction, PRX1+ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1+ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.

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“…Clusters representing mpMSC, dpMSC, osteoprogenitor cells, osteoblasts, and proliferating BMSCs were identified in bone marrow. mpMSCs were placed in the center of pseudo-time trajectory, which directed to proliferating BMSC, dpMSC, and osteoprogenitor cell respectively ( Sivaraj et al, 2021 ). PDGFRα + β + mpMSCs contained progenitors that gave rise to bone-forming osteoblast lineage cells, LepR + marrow stromal cells, and dpMSCs, whereas PDGFRα + dpMSCs from juvenile mice showed limited growth in vitro ( Sivaraj et al, 2021 ).…”

Section: Scrna-seq-based Msc Identification and Function Assessmentmentioning

confidence: 99%

Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis

Shen

Shi

2022

Front. Cell Dev. Biol.

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Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.

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Regional specialization and fate specification of bone stromal cells in skeletal development

Cited by 64 publications

References 67 publications

Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing

Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing

Tracing PRX1+ cells during molar formation and periodontal ligament reconstruction

Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis

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