Dataset Information

Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules.

ABSTRACT: Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue-specific lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating molecules can modulate the stem cell's developmental program, and thus potentially overcome the limited lineage differentiation that human stem cells exhibit based on the source and processing of stem cells. In this study, we screened a library of 84 small molecule pharmacological agents indicated in nucleosomal modification and identified a sub-set of specific molecules that influenced osteogenesis in human mesenchymal stem cells (hMSCs) while maintaining cell viability in-vitro. Pre-treatment with five candidate hits, Gemcitabine, Decitabine, I-CBP112, Chidamide, and SIRT1/2 inhibitor IV, maximally enhanced osteogenesis in-vitro. In contrast, five distinct molecules, 4-Iodo-SAHA, Scriptaid, AGK2, CI-amidine and Delphidine Chloride maximally inhibited osteogenesis. We then tested the role of these molecules on hMSCs derived from aged human donors and report that small epigenetic molecules, namely Gemcitabine and Chidamide, can significantly promote osteogenic differentiation by 5.9- and 2.3-fold, respectively. Taken together, this study demonstrates new applications of identified small molecule drugs for sensitively regulating the lineage plasticity fates of bone-marrow derived mesenchymal stem cells through modulating the epigenetic profile of the cells.

SUBMITTER: Dhaliwal A

PROVIDER: S-EPMC6215020 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules.

Dhaliwal Anandika A Pelka Sandra S Gray David S DS Moghe Prabhas V PV

Scientific reports 20181102 1

Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue-specific lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating molecules can modulate the stem cell's developmental program, and thus potentially overcome the limited lineage differentiation that human stem cells exhibit base ...[more]

PMID: 30389989

Similar Datasets

Project description:Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the characteristics of hEndSCs that were isolated from two sources: endometrium and menstrual blood, which both contain endometrial origin stem cells. Changes in gene and protein expression levels during long-term cultivation and decidualization potential were examined in endometrial stem cells (EndSCs) and menstrual blood stem cells (MenSCs). The decidualization process was induced on early and late passages of hEndSCs using dibutyryl cyclic-AMP (db-cAMP) and medroxyprogesterone acetate (MPA) agents. We demonstrated that after long-term cultivation of hEndSCs the expression of typical mesenchymal stromal cell surface markers such as CD44, CD73, CD90, CD105 and perivascular marker CD146 remains at a similar level throughout long-term cultivation. Additionally, hematopoietic and endothelial markers CD34, CD45 were also tested, they were negative in all cases. Analyzed stem cells gene markers, such as OCT4, SOX2, NANOG, KLF4, showed similar expression in all passages of hEndSCs. RT-qPCR results demonstrated that the expression of cell cycle control associated genes - CDK2, CCNA2, CCNE2, p21, p53 and Rb, among all groups was very similar. Expression of genes associated with senescence (ATM, JUND, TOP2A, MYC) was maintained at a similar level throughout passaging. In addition, Western blot analysis was used to assess changes in proteins' levels associated to epigenetics (EZH2, SUZ12, H3K27me3) and cell cycle control (cyclinE1, p53) during long-term cultivation. The levels of proteins associated with epigenetic changes were fluctuated slightly depending on the patient. Also, we demonstrated that in all induced hEndSCs the expression of decidualization markers Prolactin (PRL), IGFBP1 and WNT4 was upregulated. In conclusion, we demonstrated successful decidualization of stem cells derived from two reproductive system resources: endometrium and menstrual blood by using db-cAMP and MPA regardless of the length of the stem cell passaging. According these findings, we suppose that endometrium derived stem cells and menstrual blood derived stem cells could have a potency not only for endometrium tissue regeneration, but could also become a successful therapy for reproductive system disorders, including infertility or recurrent pregnancy loss.

Dataset Information

Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules.

Publications

Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets