Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis

Rauch, Alexander; Haakonsson, Anders K; Madsen, Jesper Grud Skat; Kobæk-Larsen, Morten; Forss, Isabel; Madsen, Martin Rønn; Hauwaert, Elvira Laila Van; Wiwie, Christian; Jespersen, Naja Zenius; Tencerová, Michaela; Nielsen, Ronni; Larsen, Bjørk Ditlev; Röttger, Richard; Baumbach, Jan; Schéele, Camilla; Kassem, Moustapha; Mandrup, Susanne

doi:10.1038/s41588-019-0359-1

Cited by 189 publications

(223 citation statements)

References 89 publications

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“…1C). Our observation that adipogenic differentiation is accompanied with more changes in TFs than osteogenic differentiation is consistent with a recent analysis of in vitro adipogenic and osteogenic differentiation of human MSC-TERT4 cells 25 .…”

Section: The Osteogenic and Adipogenic Lineage Commitment Of Bone Marsupporting

confidence: 93%

“…Apparently, compared to them, MERAs possess a completely different set of functions. Why bone marrow mesenchymal progenitors need to turn on adipocyte transcriptome in order to become a central regulator of bone marrow environment is an 25 interesting question. Furthermore, future studying the underlying molecular mechanisms by which they regulate their environment will shed light on identifying new drugs for treating bone diseases such as osteoporosis.…”

Section: Mscs In Bone Marrow Is Still Ambiguous Since Lepr + Cells Amentioning

confidence: 99%

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

Zhong

Yao

Tower

et al. 2019

Preprint

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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 mesenchymal stem cells (MSCs), the true identity of MSCs and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing single cell transcriptome analysis, we identified MSCs and delineated their bilineage differentiation paths in young, adult and aging mice. Among several newly discovered mesenchymal subpopulations, one is a distinct population of adipose-lineage cells that we named marrow environment regulating adipose cells (MERAs). MERAs are non-proliferative, postprogenitor cells that express many mature adipocyte markers but are devoid of lipid droplets. They are abundant in the bone marrow of young mice, acting as pericytes and stromal cells that form numerous connections among themselves and with other cells inside bone, including endothelial cells. Genetic ablation of MERAs disrupts marrow vessel structure, promotes de novo bone formation. Taken together, MERAs represent a unique population of adipose lineage cells that exist only in the bone marrow with critical roles in regulating bone and vessel homeostasis.

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Section: The Osteogenic and Adipogenic Lineage Commitment Of Bone Marsupporting

confidence: 93%

Section: Mscs In Bone Marrow Is Still Ambiguous Since Lepr + Cells Amentioning

confidence: 99%

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

Zhong

Yao

Tower

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…These axes aredefined by an existing range of cell types and the projection would determine whether a perturbation has shifted the genome contacts along one of the key directions identified by the E-PC space. This is conceptually analogous to previously published tracking of cell differentiation or epithelial to mesenchymal transitions along gene expression PCA spaces [26], [27], but would give a picture of whether genome contact changes in such conditions match the expected progression toward chromosome structure characteristics of other cell types.…”

Section: Discussionmentioning

confidence: 56%

3D Genome Structure Variation Across Cell Types Captured by Integrating Multi-omics

Shen

McCord

2019

Preprint

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Background3D genome structure contributes to the establishment or maintenance of cell identity in part by organizing genes into spatial active or inactive compartments. Less is known about how compartment switching occurs across different cell types. Rather than analyze individual A/B compartment switches between pairs of cell types, here, we seek to identify coordinated changes in groups of compartment-scale interactions across a spectrum of cell types. ConclusionOur results suggest that cells adapt their chromosome structures, guided by variable associations with the lamina and histone marks, to allocate up-regulatory or down-regulatory resources to certain regions and achieve transcription and chromatin accessibility variation. Our study shows E-PCA can identify the major variable interaction sets within populations of single cells, across broad categories of normal cell types, and between cancer and non-cancerous cell types.

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“…Osteoblast is responsible for bone formation, [24][25][26] and MC3T3-E1 cells are precursors of osteoblasts. Since IL-10 regulates arthritis development, 12,13 we speculated that IL-10 is involved in the osteogenic capacity of MC3T3-E1 cells.…”

Section: Il-10 Targets Both Innate and Adaptive Immune Responses And Ex-mentioning

confidence: 99%

IL‐10 induces MC3T3‐E1 cells differentiation towards osteoblastic fate in murine model

Xiong

Yan

Chen

et al. 2019

J Cellular Molecular Medi

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Interleukin‐10 (IL‐10) displays well‐documented anti‐inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL‐10 negatively regulates microRNA‐7025‐5p (miR‐7025‐5p), the down‐regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin‐like growth factor 1 receptor (IGF1R) is a miR‐7025‐5p target gene that positively regulates osteoblast differentiation. In vivo studies indicated that the pre‐injection of IL‐10 leads to increased bone formation, while agomiR‐7025‐5p injection delays fracture healing. Taken together, these results indicate that IL‐10 induces osteoblast differentiation via regulation of the miR‐7025‐5p/IGF1R axis. IL‐10 therefore represents a promising therapeutic strategy to promote fracture healing.

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Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis

Cited by 189 publications

References 89 publications

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

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

3D Genome Structure Variation Across Cell Types Captured by Integrating Multi-omics

IL‐10 induces MC3T3‐E1 cells differentiation towards osteoblastic fate in murine model

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