Alterations of Chromatin Accessibility of Human Mesenchymal Stem Cells During Early Differentiation Stage Toward Osteoblasts and Adipocyte

Abstract Although differential expression of genes is apparent during the adipogenic/osteogenic differentiation of marrow mesenchymal stem cells (MSCs), it is not known whether this is associated with changes in chromosomal structure. In this study, we used ATAC-sequencing technology to observe variations in chromatin assembly during the early stages of MSC differentiation. This showed significant changes in the number and distribution of chromosome accessibility at different time points of adipogenic/osteogenic differentiation. Sequencing of differential peaks indicated alterations in transcription factor motifs involved in MSC differentiation. Gene Ontology (GO) and pathway analysis indicated that changes in biological function resulted from the alterations in chromatin accessibility. We then integrated ATAC-seq and RNA-seq and found that only a small proportion of the overlapped genes were screened out from ATAC-seq and RNA-seq overlapping. Through GO and pathway analysis of these overlapped genes, we not only observed some known biological functions related to adipogenic/osteogenic differentiation but also noticed some unusual biological clustering during MSC differentiation. In summary, our work not only presents the landscape of chromatin accessibility of MSC during differentiation but also helps to further our understanding of the underlying mechanisms of gene expression in these processes.

Download Full-text

Dihydroartemisinin Promotes the Osteogenesis of Human Mesenchymal Stem Cells via the ERK and Wnt/β-Catenin Signaling Pathways

BioMed Research International ◽

10.1155/2019/3456719 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Licheng Ni ◽

Zhihui Kuang ◽

Zhe Gong ◽

Deting Xue ◽

Qiang Zheng

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Signaling Pathways ◽

Artemisia Annua ◽

Human Mesenchymal Stem Cells ◽

Biological Functions ◽

Low Toxicity ◽

Underlying Mechanisms ◽

Important Drug

Dihydroartemisinin (DHA), which is considered to be one of the active compounds within Artemisia annua, has extensively been used in recent years as the most effective drug against malaria, having many biological functions including anticancer, antifungal, and immunomodulatory activities. However, DHA plays a role in the regulation of the proliferation and human mesenchymal stem cells (hMSCs) osteogenic differentiation that remains unknown. We explored DHA’s effect on hMSCs’ proliferation as well as the osteogenic differentiation, together with its underlying mechanisms of action. We showed that DHA enhanced osteogenic differentiation but had no significant effect on hMSCs’ proliferation. It probably exerted its functions through the signaling pathways of ERK1/2 as well as Wnt/β. Because DHA has low toxicity and costs, it might be regarded as an important drug for fracture treatment and tissue engineering.

Download Full-text

Faculty Opinions recommendation of CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7299957.7553056 ◽

2010 ◽

Author(s):

Louise Purton ◽

Emma Baker

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Human Mesenchymal Stem Cells

Download Full-text

Wnt7a Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells

SSRN Electronic Journal ◽

10.2139/ssrn.3369750 ◽

2019 ◽

Author(s):

Leiluo Yang ◽

Qing Li ◽

Junhong Zhang ◽

Pengcheng Li ◽

Chaoliang Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Human Mesenchymal Stem Cells

Download Full-text

Fluid Flow Mechanical Stimulation-Assisted Cartridge Device for the Osteogenic Differentiation of Human Mesenchymal Stem Cells

Micromachines ◽

10.3390/mi12080927 ◽

2021 ◽

Vol 12 (8) ◽

pp. 927

Author(s):

Ki-Taek Lim ◽

Dinesh-K. Patel ◽

Sayan-Deb Dutta ◽

Keya Ganguly

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Fluid Flow ◽

Osteogenic Differentiation ◽

Flow Condition ◽

Cultured Cells ◽

Human Mesenchymal Stem Cells ◽

Proliferation And Differentiation ◽

Static Conditions

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into different types of mesodermal tissues. In vitro proliferation and differentiation of hMSCs are necessary for bone regeneration in tissue engineering. The present study aimed to design and develop a fluid flow mechanically-assisted cartridge device to enhance the osteogenic differentiation of hMSCs. We used the fluorescence-activated cell-sorting method to analyze the multipotent properties of hMSCs and found that the cultured cells retained their stemness potential. We also evaluated the cell viabilities of the cultured cells via water-soluble tetrazolium salt 1 (WST-1) assay under different rates of flow (0.035, 0.21, and 0.35 mL/min) and static conditions and found that the cell growth rate was approximately 12% higher in the 0.035 mL/min flow condition than the other conditions. Moreover, the cultured cells were healthy and adhered properly to the culture substrate. Enhanced mineralization and alkaline phosphatase activity were also observed under different perfusion conditions compared to the static conditions, indicating that the applied conditions play important roles in the proliferation and differentiation of hMSCs. Furthermore, we determined the expression levels of osteogenesis-related genes, including the runt-related protein 2 (Runx2), collagen type I (Col1), osteopontin (OPN), and osteocalcin (OCN), under various perfusion vis-à-vis static conditions and found that they were significantly affected by the applied conditions. Furthermore, the fluorescence intensities of OCN and OPN osteogenic gene markers were found to be enhanced in the 0.035 mL/min flow condition compared to the control, indicating that it was a suitable condition for osteogenic differentiation. Taken together, the findings of this study reveal that the developed cartridge device promotes the proliferation and differentiation of hMSCs and can potentially be used in the field of tissue engineering.

Download Full-text