- Adipose-Derived Stem/Stromal Cells Recapitulate Aging Biomarkers and Show Reduced Stem Cell Plasticity Affecting Their Adipogenic Differentiation Capacity. [Journal Article]
- CRCell Reprogram 2019 Jul 12
- Stromal mesenchymal stem cells (MSCs) have the capability to self-renew and can differentiate into multiple cell types of the mesoderm germ layer, but their properties are affected by molecular aging…
Stromal mesenchymal stem cells (MSCs) have the capability to self-renew and can differentiate into multiple cell types of the mesoderm germ layer, but their properties are affected by molecular aging mechanisms. MSCs can be obtained from adipose tissue termed as adipose-derived stem/stromal cells (ASCs) representing a promising tool for studying age-related diseases in detail. ASCs from young (16 weeks) and old (>108 weeks) rabbits were successfully isolated and propagated. ASCs showed the typical morphology and stained positive for CD105, Vimentin, Collagenase 1A, and negative for CD14, CD90, and CD73, demonstrating their mesenchymal origin. ASCs expressed MSC markers, including MYC, KLF4, CHD1, REST, and KAT6A, whereas pluripotency-related genes, such as NANOG, OCT4, and SOX2, were not expressed. Aged ASCs showed altered protein and mRNA levels of APOE, ATG7, FGF2, PTEN, and SIRT1. Adipogenic differentiation of old visceral ASCs was significantly decreased compared with young visceral ASCs. We successfully established rabbit ASC cultures representing an in vitro model for the analysis of stem cell aging mechanisms. ASCs, obtained from old female rabbits, showed age- and source-specific alteration due to aging of the donor. Stem cell plasticity was altered with age as shown by reduced adipogenic differentiation capacity.
- Effect of aging on behaviour of mesenchymal stem cells. [Review]
- WJWorld J Stem Cells 2019 Jun 26; 11(6):337-346
- Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives (chondrocytes, osteocytes, adipocytes). This subpopulatio…
Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives (chondrocytes, osteocytes, adipocytes). This subpopulation of adult stem cells, called "mesenchymal stem cells" or "mesenchymal stromal cells (MSCs)", contributes directly to the homeostatic maintenance of their organs; hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.
- VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type I receptor degradation. [Journal Article]
- JMJ Mol Cell Biol 2019 Jul 10
- The transforming growth factor-β (TGF-β) family controls embryogenesis, stem cell differentiation and tissue homeostasis. However, how post-translation modifications contribute to fine-tuning of TGF-…
The transforming growth factor-β (TGF-β) family controls embryogenesis, stem cell differentiation and tissue homeostasis. However, how post-translation modifications contribute to fine-tuning of TGF-β family signaling responses is not well understood. Inhibitory (I)-Smads can antagonize TGF-β/Smad signaling by recruiting Smurf E3 ubiquitin ligases to target the active TGF-β receptor for proteasomal degradation. A proteomic interaction screen identified Vpr binding protein (VprBP) as novel binding partner of I-Smad7. Mis-expression studies revealed that VprBP negatively controls Smad2 phosphorylation, Smad2-Smad4 interaction, as well as TGF-β target gene expression. VprBP was found to promote Smad7-Smurf1-TβRI complex formation and induce proteasomal degradation of TGF-β type I receptor (TβRI). Moreover, VprBP appears to stabilize Smurf1 by suppressing Smurf1 poly-ubiquitination. In multiple adult and mouse embryonic stem cells, depletion of VprBP promotes TGF-β or Activin-induced responses. In the mouse embryo VprBP expression negatively correlates with mesoderm marker expression, and VprBP attenuated mesoderm induction during zebrafish embryogenesis. Our findings thereby uncover a novel regulatory mechanism by which Smurf1 controls the TGF-β and Activin cascade and identify VprBP as a critical determinant of embryonic mesoderm induction.
- Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18). [Journal Article]
- DDDev Dyn 2019 Jul 10
- CONCLUSIONS: These alleles will be useful to investigate FGF18 function during organogenesis and tissue homeostasis, and to target specific cell lineages at embryonic and postnatal time points. This article is protected by copyright. All rights reserved.
- Concise Review: Application of tonsil-derived mesenchymal stem cells in tissue regeneration. [Journal Article]
- SCStem Cells 2019 Jul 09
- Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have…
Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have been widely used in various research application, yet there are limitations such as invasiveness of obtaining samples, low yield and proliferation rates, and questions regarding their practicality in clinical applications. Some have suggested that MSCs from other sources, specifically those derived from palatine tonsil tissues, that is, tonsil-derived MSCs (TMSCs), could be considered as a new potential therapeutic tool in regenerative medicine due to their superior proliferation rate and differentiation capabilities with low immunogenicity and ease of obtaining. Several studies have determined that TMSCs have differentiation potentials not only into the mesoderm lineage but also into the endodermal as well as ectodermal lineages, expanding their potential usage and placing them as an appealing option to consider for future studies in regenerative medicine. In this review, the differentiation capacities of TMSCs and their therapeutic competencies from past studies are addressed. SIGNIFICANCE STATEMENT: Mesenchymal stem cells (MSCs) are considered as a great candidate for tissue engineering in regenerate medicine. Tonsil-derived MSCs (TMSCs) could be an attractive option for clinical applications because of their non-invasiveness of tissue collection, relatively high proliferation rate, and low allogenicity. This review addresses potential differentiation capabilities of TMSCs into mesodermal, endodermal, and ectodermal lineages reported from previous in vitro and in vivo studies as well as their potential applications for treating various human diseases. © AlphaMed Press 2019.
- [Application of Intermediate Mesoderm-like Cells in Kidney Regeneration]. [Journal Article]
- ZYZhongguo Yi Xue Ke Xue Yuan Xue Bao 2019 Jun 30; 41(3):291-299
- Objective To induce adipose-derived stem cells (ADSCs) to differentiate into intermediate mesoderm (IM)-like cells in vitro,with IM-like cells for recellularizing kidney scaffolds,and then to obtain …
Objective To induce adipose-derived stem cells (ADSCs) to differentiate into intermediate mesoderm (IM)-like cells in vitro,with IM-like cells for recellularizing kidney scaffolds,and then to obtain a tissue-engineering kidney with renal structures and functions through co-culture.Methods After inguinal fat pads of Wistar rats were surgically harvested,the primary ADSCs were isolated,induced,and cultured for stem cell identification. ADSCs were inducted to differentiate into IM-like cells by adding glycogen synthase kinase-3 inhibitor (CHIR99021) and fibroblast growth factor 9 (FGF9) at different stages. Seven days later,the IM-like cells were identified. The induced IM-like cells and well-prepared kidney decellularized scaffolds were co-cultured for 10 days to obtain recellularized tissue-engineered kidneys and their differentiation was identified.Results The ADSCs harvested had osteogenic and adipogenic abilities and could express the stem cell surface markers. After 7 days of in vitro induction,the positive expressions of odd-skipped related 1 and paired-box 2 were observed in IM-like cells by immunofluorescence technique. After 10 days of co-culture with kidney decellularized scaffolds,the positive expressions of Wilms'tumor 1,GATA-binding protein-3,and E-cadherin were observed by immunofluorescence technique.Conclusion ADSCs can be induced into IM-like cells,and renal cell differentiation can be observed through combining the induced IM-like cells with kidney decellularized scaffolds.
- Mechanical impact of epithelial-mesenchymal transition on epithelial morphogenesis in Drosophila. [Journal Article]
- NCNat Commun 2019 Jul 04; 10(1):2951
- Epithelial-mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. Intriguingly, EMT is often associated with tissue invagination during development; how…
Epithelial-mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. Intriguingly, EMT is often associated with tissue invagination during development; however, the impact of EMT on tissue remodeling remain unexplored. Here, we show that at the initiation of the EMT process, cells produce an apico-basal force, orthogonal to the surface of the epithelium, that constitutes an important driving force for tissue invagination in Drosophila. When EMT is ectopically induced, cells starting their delamination generate an orthogonal force and induce ectopic folding. Similarly, during mesoderm invagination, cells undergoing EMT generate an apico-basal force through the formation of apico-basal structures of myosin II. Using both laser microdissection and in silico physical modelling, we show that mesoderm invagination does not proceed if apico-basal forces are impaired, indicating that they constitute driving forces in the folding process. Altogether, these data reveal the mechanical impact of EMT on morphogenesis.
- CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock. [Journal Article]
- EREMBO Rep 2019; 20(7):e46436
- All vertebrates share a segmented body axis. Segments form from the rostral end of the presomitic mesoderm (PSM) with a periodicity that is regulated by the segmentation clock. The segmentation clock…
All vertebrates share a segmented body axis. Segments form from the rostral end of the presomitic mesoderm (PSM) with a periodicity that is regulated by the segmentation clock. The segmentation clock is a molecular oscillator that exhibits dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanism by which NICD stability is regulated in this context is unclear. We identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations and an increase in somite size.
- Correction: From Dynamic Expression Patterns to Boundary Formation in the Presomitic Mesoderm. [Published Erratum]
- PCPLoS Comput Biol 2019; 15(7):e1007191
- [This corrects the article DOI: 10.1371/journal.pcbi.1002586.].
[This corrects the article DOI: 10.1371/journal.pcbi.1002586.].
New Search Next
- Genetic regulation of amphioxus somitogenesis informs the evolution of the vertebrate head mesoderm. [Journal Article]
- NENat Ecol Evol 2019 Jul 01
- The evolution of vertebrates from an ancestral chordate was accompanied by the acquisition of a predatory lifestyle closely associated to the origin of a novel anterior structure, the highly speciali…
The evolution of vertebrates from an ancestral chordate was accompanied by the acquisition of a predatory lifestyle closely associated to the origin of a novel anterior structure, the highly specialized head. While the vertebrate head mesoderm is unsegmented, the paraxial mesoderm of the earliest divergent chordate clade, the cephalochordates (amphioxus), is fully segmented in somites. We have previously shown that fibroblast growth factor signalling controls the formation of the most anterior somites in amphioxus; therefore, unravelling the fibroblast growth factor signalling downstream effectors is of crucial importance to shed light on the evolutionary origin of vertebrate head muscles. By using a comparative RNA sequencing approach and genetic functional analyses, we show that several transcription factors, such as Six1/2, Pax3/7 and Zic, act in combination to ensure the formation of three different somite populations. Interestingly, these proteins are orthologous to key regulators of trunk, and not head, muscle formation in vertebrates. Contrary to prevailing thinking, our results suggest that the vertebrate head mesoderm is of visceral and not paraxial origin and support a multistep evolutionary scenario for the appearance of the unsegmented mesoderm of the vertebrates new 'head'.