scholarly journals ATF4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Daniel M Cohen ◽  
Kyoung-Jae Won ◽  
Nha Nguyen ◽  
Mitchell A Lazar ◽  
Christopher S Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Dna Sequence ◽  
Cell Shape ◽  
Chemical Cues ◽  
Adipocyte Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Seeding Density ◽  
Transcriptional Program

A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing transcription in human mesenchymal stem cells (hMSCs) adipogenically primed by confluence. Prior to adipogenesis, confluency promotes heterodimer recruitment of the bZip TFs C/EBPβ and ATF4 to a non-canonical C/EBP DNA sequence. ATF4 depletion decreases both cell-density-dependent transcription and adipocyte differentiation. Global profiling in hMSCs and a novel cell-free assay reveals that ATF4 requires C/EBPβ for genomic binding at a motif distinct from that bound by the C/EBPβ homodimer. Our observations demonstrate that C/EBPβ bridges the transcriptional programs in naïve, confluent cells and early differentiating pre-adipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPβ to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.

scholarly journals The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes

2018 ◽  
Vol 19 (7) ◽  
pp. 2081 ◽  
Author(s):  
Christian Carpéné ◽  
Héctor Pejenaute ◽  
Raquel del Moral ◽  
Nathalie Boulet ◽  
Elizabeth Hijona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phenolic Compounds ◽  
Glucose Transport ◽  
Adipocyte Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Herbal Remedies ◽  
Metabolic Complications ◽  
Obesity And Diabetes

Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.

scholarly journals PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shuchi Agrawal Singh ◽  
Mads Lerdrup ◽  
Ana-Luisa R Gomes ◽  
Harmen JG van de Werken ◽  
Jens Vilstrup Johansen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Osteogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
High Expression ◽  
Molecular Function

The PLZF transcription factor is essential for osteogenic differentiation of hMSCs; however, its regulation and molecular function during this process is not fully understood. Here, we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naive hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation.

scholarly journals Role of Slug transcription factor in human mesenchymal stem cells

2012 ◽  
Vol 16 (4) ◽  
pp. 740-751 ◽  
Author(s):  
Elena Torreggiani ◽  
Gina Lisignoli ◽  
Cristina Manferdini ◽  
Elisabetta Lambertini ◽  
Letizia Penolazzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Human Mesenchymal Stem Cells

scholarly journals On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

2020 ◽  
Author(s):  
Aliaksei S Vasilevich ◽  
Steven S Vermeulen ◽  
Marloes Kamphuis ◽  
Nadia Roumans ◽  
Said Eroume ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Shape ◽  
Cell Function ◽  
Phenotypic Diversity ◽  
Human Mesenchymal Stem Cells ◽  
Early Response ◽  
Cell Physiology ◽  
Cell Shapes ◽  
Open Question

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. Thus, we have started to unravel the open question of how cell function follows cell shape. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

scholarly journals Mapping SOX9 transcriptional dynamics during multi-lineage differentiation of human mesenchymal stem cells

2021 ◽  
Author(s):  
Kannan Govindaraj ◽  
Sakshi Khurana ◽  
Marcel Karperien ◽  
Janine Nicole Post
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Single Cell ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Transcriptional Dynamics

The master transcription factor SOX9 is a key player during chondrocyte differentiation, cartilage development, homeostasis and disease. Modulation of SOX9 and its target gene expression is essential during chondrogenic, osteogenic and adipogenic differentiation of human mesenchymal stem cells (hMSCs). However, lack of sufficient knowledge about the signaling interplay during differentiation remains one of the main reasons preventing successful application of hMSCs in regenerative medicine. We previously showed that Transcription Factor - Fluorescence Recovery After Photobleaching (TF-FRAP) can be used to study SOX9 dynamics at the single cell level. We showed that changes in SOX9 dynamics are linked to its transcriptional activity. Here, we investigated SOX9 dynamics during differentiation of hMSCs into the chondrogenic, osteogenic and adipogenic lineages. We show that there are clusters of cells in hMSCs with distinct SOX9 dynamics, indicating that there are a number of subpopulations present in the heterogeneous hMSCs. SOX9 dynamics data at the single cell resolution revealed novel insights about its activity in these subpopulations (cell types). In addition, the response of SOX9 to differentiation stimuli varied in these subpopulations. Moreover, we identified donor specific differences in the number of cells per cluster in undifferentiated hMSCs, and this correlated to their differentiation potential.

scholarly journals On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aliaksei S. Vasilevich ◽  
Steven Vermeulen ◽  
Marloes Kamphuis ◽  
Nadia Roumans ◽  
Said Eroumé ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Shape ◽  
Cell Function ◽  
Phenotypic Diversity ◽  
Human Mesenchymal Stem Cells ◽  
Early Response ◽  
Cell Physiology ◽  
Quantitative Image ◽  
Cell Shapes

Abstract Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

scholarly journals Factors Influencing the Successful Isolation and Expansion of Aging Human Mesenchymal Stem Cells

2018 ◽  
Vol 13 (1) ◽  
pp. 279-284
Author(s):  
Pan Pan Chong ◽  
Lakshmi Selvaratnam ◽  
Azlina A. Abbas ◽  
Tunku Kamarul
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Medical Information ◽  
Human Mesenchymal Stem Cells ◽  
Statistical Correlation ◽  
Seeding Density ◽  
Successful Isolation ◽  
Demographic Background ◽  
Ageing Populations

AbstractMost studies highlight mesenchymal stem cells (MSCs) extracted primarily from bone marrow (BM), very few report the use of peripheral blood (PB), often due to the associated low seeding density and difficulties with extraction techniques. As ageing populations are becoming more predominant globally, together with escalating demands for MSC transplantation and tissue regeneration, obtaining quality MSCs suitable for induced differentiation and biological therapies becomes increasingly important. In this study, BM and PB were obtained from elderly patients and extracted MSCs grown in vitro to determine their successful isolation and expansion. Patients’ socio-demographic background and other medical information were obtained from medical records. Successful and failed cultures were correlated with key demographic and medical parameters. A total of 112 samples (BM or PB) were used for this study. Of these, 50 samples (44.6%) were successfully cultured according to standardised criteria with no signs of contamination. Our comparative analyses demonstrated no statistical correlation between successful MSC cultures and any of the six demographic or medical parameters examined, including sample quantity, age, sex, race, habits and underlying comorbidities of sample donors. In conclusion, the present study demonstrates that typical demographics and comorbidities do not influence successful MSC isolation and expansion in culture.

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