Genome-wide analysis of familial dysautonomia and kinetin target genes with patient olfactory ecto-mesenchymal stem cells

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes inin vitroglucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1−/−). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1−/−cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1−/−lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1−/−compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications.

Download Full-text

miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells

Cellular Physiology and Biochemistry ◽

10.1159/000495489 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1087-1102 ◽

Cited By ~ 9

Author(s):

Lijun Duan ◽

He Zhao ◽

Yang Xiong ◽

Xiangsheng Tang ◽

Yongdong Yang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Osteoblast Differentiation ◽

Target Genes ◽

Fragility Fractures ◽

Inhibitory Effect ◽

Lymphocytic Leukemia ◽

Qrt Pcr ◽

Wnt Signal

Background/Aims: Osteoporosis is a bone metabolic disease characterized by a systemic impairment of bone mass, which results in increased propensity of fragility fractures. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. Mesenchymal stem cells (MSCs) are induced to differentiate into preosteoblasts, which are regulated by the signaling cascades initiated by the various signals, including miRNAs. miR-16-2* is a newly discovered miRNA that participates in diagnosis and prognosis of hepatocellular carcinoma, cervical cancer and chronic lymphocytic leukemia. However, the effect of miR-16-2* on the regulation of osteoblast differentiation and the mechanism responsible are still unclear. Here we discuss the contribution of miR-16-2* to osteoporosis, osteoblast differentiation and mineralization. Methods: The expression pattern of miR-16-2* during osteogenesis or in osteoporosis bone samples was validated by quantitative real-time PCR (qRT-PCR). The human bone marrow mesenchymal stem cells (hBMSCs) were induced to differentiate into osteoblasts by osteogenic induced medium containing dexamethasone, ascorbate-2-phosphat, beta-glycerophosphate and vitamin-D3. The target genes of miR-16-2* were predicted by TargetScan and PicTar. The mRNA and protein levels of osteogenic key markers were detected using qRT-PCR or western blot respectively. The WNT signal activity was analyzed by TOP/FOP reporter assay. Results: The expression of miR-16-2* in patient bone tissue with osteoporosis was negatively correlated with bone formation related genes. During osteoblast differentiation process, the expression of miR-16-2* was significantly decreased. Upregulation of miR-16-2* in hBMSCs impaired the osteogenic differentiation while the downregulation of miR-16-2* increased this process. Upregulation the expression of miR-16-2* could also block the WNT signal pathway by directly target WNT5A. Furthermore, knockdown of miR-16-2* could promote the activation of RUNX2, possibly by lifting the inhibitory effect of miR-16-2* on WNT pathway. Conclusion: Taken together, we report a novel biological role of miR-16-2* in osteogenesis through regulating WNT5A response for the first time. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

Download Full-text

Genome-Wide Analysis Reveals PADI4 Facilitates Transcriptional Activation of a Subset of Elk-1 Target Genes in MCF-7 Cells.

10.1210/endo-meetings.2010.part1.p3.p1-108 ◽

2010 ◽

pp. P1-108-P1-108

Author(s):

XS Zhang ◽

MJ Gamble ◽

S Stadler ◽

BD Cherrington ◽

MS Roberson ◽

...

Keyword(s):

Transcriptional Activation ◽

Target Genes ◽

Genome Wide Analysis ◽

Genome Wide ◽

Mcf 7

Download Full-text

Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

eLife ◽

10.7554/elife.02104 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 25

Author(s):

Sarina Ravens ◽

Marjorie Fournier ◽

Tao Ye ◽

Matthieu Stierle ◽

Doulaye Dembele ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Transcription Regulation ◽

Histone Acetyltransferase ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Individual Contribution ◽

Genome Wide Analysis ◽

Genome Wide ◽

The Individual

The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation.

Download Full-text