Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Pagella, Pierfrancesco; Roditi, Laura De Vargas; Stadlinger, Bernd; Moor, Andreas E.; Mitsiadis, Thimios A.

doi:10.1002/sctm.21-0086

Cited by 21 publications

(16 citation statements)

References 63 publications

(159 reference statements)

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“…Endothelial cells may interact with periodontal stem cells. Single cell RNA sequencing showed that periodontal stem cells express NOTCH3, and that the adjacent endothelial cells express all five NOTCH ligands, JAG1, JAG2, DLL1, DLL3, and DLL4, acting as niche‐derived modulator of periodontal stem cells (Pagella, de Vargas Roditi, Stadlinger, Moor, & Mitsiadis, 2021). Inhibition of Notch in vitro reduced the periodontal H type endothelium and down‐regulated coupled osteogenesis.…”

Section: Components Of Periodontal Stem Cell Nichementioning

confidence: 99%

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo

Liu

Men

et al. 2022

Genesis

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Summary Periodontium possesses stem cell populations for its self‐maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.

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Section: Components Of Periodontal Stem Cell Nichementioning

confidence: 99%

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo

Liu

Men

et al. 2022

Genesis

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“…During adulthood, Notch signalling plays an important role in regulating the behaviour of stem cells, by maintaining their stemness and influencing their fate in most tissues [17,18]. Notch signalling is active in various adult stem cell niches [19]. For example, interaction between Notch1 and Delta-like4 (Dll4) is necessary for establishing hematopoietic clusters in the aorta-gonad-mesonephros, which is the primordial niche for hematopoietic stem cells [20].…”

Section: Spheroidsmentioning

confidence: 99%

Three-Dimensional Culture Systems for Dissecting Notch Signalling in Health and Disease

Marconi

Porcheri

Trubiani

et al. 2021

IJMS

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Three-dimensional (3D) culture systems opened up new horizons in studying the biology of tissues and organs, modelling various diseases, and screening drugs. Producing accurate in vitro models increases the possibilities for studying molecular control of cell–cell and cell–microenvironment interactions in detail. The Notch signalling is linked to cell fate determination, tissue definition, and maintenance in both physiological and pathological conditions. Hence, 3D cultures provide new accessible platforms for studying activation and modulation of the Notch pathway. In this review, we provide an overview of the recent advances in different 3D culture systems, including spheroids, organoids, and “organ-on-a-chip” models, and their use in analysing the crucial role of Notch signalling in the maintenance of tissue homeostasis, pathology, and regeneration.

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“…Notch signaling is an evolutionarily conserved, intercellular, and contact-dependent signaling pathway which regulates cell fate decisions and plays a significant role during development and organogenesis [5][6][7][8][9][10]. Many studies have demonstrated the critical role of Notch signaling in cell fate determination, cell proliferation, differentiation, and apoptosis in various cell types [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Probing Notch1-Dll4 Signaling in Regulating Osteogenic Differentiation of Human Mesenchymal Stem Cells using Single Cell Nanobiosensor

Wang

Zhao

Bousraou

et al. 2022

Preprint

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Human mesenchymal stem cells (hMSCs) have great potential in cell-based therapies for tissue engineering and regenerative medicine due to their self-renewal and multipotent properties. Recent studies indicate that Notch1-Dll4 signaling is an important pathway in regulating osteogenic differentiation of hMSCs. However, the fundamental mechanisms that govern osteogenic differentiation are poorly understood due to a lack of effective tools to detect gene expression at single cell level. Here, we established a double-stranded locked nucleic acid (LNA) /DNA (LNA/DNA) nanobiosensor for gene expression analysis in single hMSC in both 2D and 3D microenvironments. We first characterized this LNA/DNA nanobiosensor and demonstrated the Dll4 mRNA expression dynamics in hMSCs during osteogenic differentiation. By incorporating this nanobiosensor with live hMSCs imaging during osteogenic induction, we performed dynamic tracking of hMSCs differentiation and Dll4 mRNA gene expression profiles of individual hMSC during osteogenic induction. Our results showed the dynamic expression profile of Dll4 during osteogenesis, indicating the heterogeneity of hMSCs during this dynamic process. We further investigated the role of Notch1-Dll4 signaling in regulating hMSCs during osteogenic differentiation. Pharmacological perturbation is applied to disrupt Notch1-Dll4 signaling to investigate the molecular mechanisms that govern osteogenic differentiation. In addition, the effects of Notch1-Dll4 signaling on hMSCs spheroids differentiation were also investigated. Our results provide convincing evidence supporting that Notch1-Dll4 signaling is involved in regulating hMSCs osteogenic differentiation. Specifically, Notch1-Dll4 signaling is active during osteogenic differentiation. Our results also showed that Dll4 is a molecular signature of differentiated hMSCs during osteogenic induction. Notch inhibition mediated osteogenic differentiation with reduced Alkaline Phosphatase (ALP) activity. Lastly, we elucidated the role of Notch1-Dll4 signaling during osteogenic differentiation in a 3D spheroid model. Our results showed that Notch1-Dll4 signaling is required and activated during osteogenic differentiation in hMSCs spheroids. Inhibition of Notch1-Dll4 signaling mediated osteogenic differentiation and enhanced hMSCs proliferation, with increased spheroid sizes. Taken together, the capability of LNA/DNA nanobiosensor to probe gene expression dynamics during osteogenesis, combined with the engineered 2D/3D microenvironment, enables us to study in detail the role of Notch1-Dll4 signaling in regulating osteogenesis in 2D and 3D microenvironment. These findings will provide new insights to improve cell-based therapies and organ repair techniques.

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Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Cited by 21 publications

References 63 publications

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo

Three-Dimensional Culture Systems for Dissecting Notch Signalling in Health and Disease

Probing Notch1-Dll4 Signaling in Regulating Osteogenic Differentiation of Human Mesenchymal Stem Cells using Single Cell Nanobiosensor

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