Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment

eLife, Journal Year: 2020, Volume and Issue: 9

Published: April 14, 2020

Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from stem cells, the true identity of progenitors their vivo bifurcated differentiation routes into osteoblasts adipocytes remain poorly understood. Here, by employing large scale single transcriptome analysis, we computationally defined at different stages delineated bi-lineage paths young, adult aging mice. One identified subpopulation unique type expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, exist abundantly pericytes stromal form ubiquitous 3D network inside cavity. Functionally play critical roles maintaining vasculature suppressing formation. Therefore, name them adipogenic (MALPs) conclude newly component adipose tissue.

Language: Английский

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Niches that regulate stem cells and hematopoiesis in adult bone marrow

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(13), P. 1848 - 1860

Published: June 18, 2021

Language: Английский

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Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 131(2)

Published: Nov. 18, 2020

Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It well known that osteogenic cells support osteoclastogenesis via production RANKL. Interestingly, our recently identified marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) form a multidimensional network bone—was computationally demonstrated be the most interactive with monocyte-macrophage through high specific expression several osteoclast regulatory factors, including Using an adipocyte-specific Adipoq-Cre label MALPs, we mice RANKL deficiency MALPs have drastic increase trabecular mass long bones vertebrae starting from 1 month age, while their cortical appears normal. This phenotype was accompanied diminished number attenuated formation at surface. Reduced signaling calvarial abolished osteolytic lesions after LPS injections. Furthermore, ovariectomized mice, elevated resorption partially MALPs. In summary, studies critical player controlling remodeling during normal metabolism pathological RANKL-dependent fashion.

Language: Английский

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Multi-omics integration in the age of million single-cell data

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(11), P. 710 - 724

Published: Aug. 20, 2021

Language: Английский

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SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(8)

Published: Feb. 17, 2021

Significance Cartilage is essential in vertebrate development and adulthood. growth plates ensure skeletal until closing at puberty, articular cartilage ensures lifelong structural functional integrity of joints. Chondrocytes build development, governed by the transcription factor SOX9. Using mouse models transcriptome profiling approaches, we show here that SOX9 also has key roles to maintain open postnatally protect adult from osteoarthritic degradation. In particular, safeguards lineage fate chondrocytes preventing their dedifferentiation into skeletogenic mesenchymal progenitors followed redifferentiation osteoblasts. These findings provide insights cellular plasticity its molecular control developmental, physiological, pathological processes within beyond system.

Language: Английский

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Bone marrow and periosteal skeletal stem/progenitor cells make distinct contributions to bone maintenance and repair

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(11), P. 1547 - 1561.e6

Published: Oct. 21, 2022

A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) marrow versus periosteum to repair. We found that SSCs adult can be identified based on Leprcre and Adiponectin-cre/creER expression while Gli1creERT2 expression. Under steady-state conditions, new arose primarily from SSCs. After injuries, both SSC populations began proliferating but made very different Drill injuries were repaired by LepR+/Adiponectin+ Conversely, bicortical fractures Gli1+ periosteal SSCs, though transiently formed trabecular at fracture site. also regenerated LepR+ stromal expressed hematopoietic niche factors sites. Different are thus with regenerating stroma after non-stabilized fractures.

Language: Английский

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Senescent immune cells release grancalcin to promote skeletal aging

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(10), P. 1957 - 1973.e6

Published: Sept. 10, 2021

Language: Английский

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Cellular Heterogeneity in Adipose Tissues

Annual Review of Physiology, Journal Year: 2021, Volume and Issue: 83(1), P. 257 - 278

Published: Feb. 10, 2021

Adipose tissue depots in distinct anatomical locations mediate key aspects of metabolism, including energy storage, nutrient release, and thermogenesis. Although adipocytes make up more than 90% adipose volume, they represent less 50% its cellular content. Here, I review recent advances genetic lineage tracing transcriptomics that reveal the identities heterogeneous cell populations constituting mouse human tissues. In addition to mature their progenitors, these include endothelial various immune types together orchestrate development functions. One salient finding is identification progenitor subtypes can modulate adipogenic capacity through paracrine mechanisms. Another description fate trajectories monocyte/macrophages, which respond maladaptively nutritional thermogenic stimuli, leading metabolic disease. These studies have generated an extraordinary source publicly available data be leveraged explore commonalities differences among experimental models, providing new insights into tissues role

Language: Английский

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RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss

EMBO Reports, Journal Year: 2021, Volume and Issue: 22(7)

Published: June 13, 2021

Language: Английский

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Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

Theranostics, Journal Year: 2022, Volume and Issue: 12(3), P. 1074 - 1096

Published: Jan. 1, 2022

Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution.The osteoimmunology microenvironment in the occurrence and development periodontitis remains poorly understood level.In this study, we used transcriptomics to comprehensively reveal complexities molecular components differences with counterparts residing periodontal tissues.Methods: We performed scRNA-seq identify 51248 single cells from healthy controls (n=4), patients severe chronic (n=5), after initial therapy within 1 month (n=3).Uniform manifold approximation projection (UMAP) were further conducted explore cellular composition tissues.Pseudotime trajectory velocity analysis, combined gene enrichment analysis pathways underlying fate decisions.CellPhoneDB ligand-receptor pairs among major types tissues.Results: A atlas tissues was characterized included ten types, such as fibroblasts, monocytic cells, endothelial T B cells.The TNFRSF21 + fibroblasts high expression CXCL1, CXCL2, CXCL5, CXCL6, CXCL13, IL24 detected compared individuals.The fractions CD55 mesenchymal stem (MSCs), APOE pre-osteoblasts (pre-OBs), IBSP osteoblasts decreased significantly response therapy.In addition, CXCL12 MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even confirmed by trajectory.Moreover, portrayed distinct subtypes abundant involved immune response.The heterogeneity characterized.Finally, mapped osteoblast/ osteoclast differentiation mediators source identifying highlighted effects Ephrin-Eph signaling on bone regeneration therapy.Conclusions: Our analyses uncovered striking spatiotemporal dynamics expression, population composition, cell-cell interactions progression.These findings provide insights underpinning regeneration.

Language: Английский

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