scholarly journals Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz1094 ◽  
Author(s):  
Bin Yao ◽  
Rui Wang ◽  
Yihui Wang ◽  
Yijie Zhang ◽  
Tian Hu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Sweat Gland ◽  
Therapeutic Potential ◽  
3D Structure ◽  
Activation Assay ◽  
3D Printed ◽  
Fate Decision ◽  
Matrix Differential ◽  
Underlying Mechanisms ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)–like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery.

scholarly journals Epigenetic Control of Mesenchymal Stromal Cell Fate Decision

2021 ◽  
Author(s):  
Haoli Ying ◽  
Ruolang Pan ◽  
Ye Chen
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Connective Tissues ◽  
Differentiation Potential ◽  
Cell Fate Decisions ◽  
Fate Decision ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering owing to their differentiation potential in various cell types. The therapeutic utility of MSCs hinges upon our understanding of the molecular mechanisms involved in cellular fate decisions. Thus, the elucidation of the regulation of MSC differentiation has attracted increasing attention in recent years. A variety of external cues contribute to the process of MSC differentiation, including chemical, physical, and biological factors. Among the multiple factors that are known to affect cell fate decisions, the epigenetic regulation of MSC differentiation has become a research hotspot. In this chapter, we summarize recent progress in the determination of the effects of epigenetic modification on the multilineage differentiation of MSCs.

scholarly journals LIX1 controls digestive mesenchyme-derived cell fate decision by regulating cristae organization in mitochondria

2022 ◽  
Author(s):  
Amandine Guerin ◽  
Claire Angebault ◽  
Sandrina Kinet ◽  
Chantal Cazevieille ◽  
Manuel Rojo ◽  
...  
Keyword(s):  
Cell Fate ◽  
Unsaturated Fatty Acids ◽  
Cell Lineage ◽  
Mitochondrial Morphology ◽  
Knock Down ◽  
Fate Decision ◽  
Underlying Mechanisms ◽  
The Stability ◽  
Mitochondrial Remodeling ◽  
Species Production

Limb Expression 1 (LIX1) is a master regulator of digestive mesenchymal progenitor and GastroIntestinal Stromal Tumor (GIST) cell proliferation by controlling the expression of the Hippo effectors YAP1/TAZ and KIT. However, the underlying mechanisms of these LIX1- mediated regulations and tumor promotion remain to be elucidated. Here, we report that LIX1 is S-palmitoylated on cysteine 84 and localized in mitochondria. LIX1 knock-down affects the mitochondrial ultrastructure, resulting in decreased respiration and mitochondrial reactive oxygen species production. This is sufficient to downregulate YAP1/TAZ and reprogram KIT- positive GIST cells towards the smooth muscle cell lineage with reduced proliferative and invasive capacities. Mechanistically, LIX1 knock-down impairs the stability of the mitochondrial proteins PHB2 and OPA1 that are found in complexes with mitochondrial- specific phospholipids and are required for cristae organization. Supplementation with unsaturated fatty acids counteracts the effects of LIX1 knock-down on mitochondrial morphology and ultrastructure, restores YAP1/TAZ signaling, and consequently KIT levels. Altogether, our findings demonstrate that LIX1 contributes to GIST aggressive potential by modulating YAP1/TAZ and KIT levels, a process that depends on mitochondrial remodeling. Our work brings new insights into the mechanisms that could be targeted in tumors in which YAP1 and TAZ are implicated.

scholarly journals Polarized endosome dynamics engage cytosolic Par-3 and dynein during asymmetric division

2020 ◽  
Author(s):  
Xiang Zhao ◽  
Kai Tong ◽  
Xingye Chen ◽  
Bin Yang ◽  
Qi Li ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Radial Glia ◽  
Asymmetric Cell Division ◽  
Time Lapse ◽  
Cell Fate Decisions ◽  
Dynein Motor ◽  
Fate Decision ◽  
Underlying Mechanisms

AbstractAsymmetric cell division (ACD), which produces two daughters with different fates, is fundamental for generating cellular diversity. In the developing embryos of both invertebrates and vertebrates, asymmetrically dividing progenitors generate daughter cells with differential activity of Notch signaling1–7, a key regulator of cell fate decisions8,9. The cell polarity regulator Par-3 is critical for establishing this Notch asymmetry1,4,6, but the underlying mechanisms are not understood. Here, employing in vivo time-lapse imaging in the developing zebrafish forebrain during the mitotic cycle of radial glia, the principal vertebrate neural stem cells10,11, we show that during ACD, endosomes containing the Notch ligand Delta D (Dld) undergo convergent movement toward the cleavage plane, followed by preferential segregation into the posterior (and subsequently basal) Notchhi daughter. This asymmetric segregation requires the activity of Par-3 and the dynein motor complex. Employing label-retention expansion microscopy, we further detect Par-3 in the cytosol in association with the dynein light intermediate chain 1 (DLIC1) on Dld endosomes, suggesting a direct involvement of Par-3 in dynein-mediated polarized transport of Notch signaling endosomes. Our data reveal an unanticipated mechanism by which Par-3 regulates cell fate decision by directly polarizing Notch signaling components during ACD.

scholarly journals Runx1 regulates embryonic myeloid fate choice in zebrafish through a negative feedback loop inhibiting Pu.1 expression

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5239-5249 ◽  
Author(s):  
Hao Jin ◽  
Li Li ◽  
Jin Xu ◽  
Fenghua Zhen ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Wide Spectrum ◽  
Negative Feedback Loop ◽  
Fate Decision ◽  
Underlying Mechanisms ◽  
Regulatory Loop

Abstract Proper cell fate choice in myelopoiesis is essential for generating correct numbers of distinct myeloid subsets manifesting a wide spectrum of subset-specific activities during development and adulthood. Studies have suggested that myeloid fate choice is primarily regulated by transcription factors; however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. Zebrafish embryonic myelopoiesis gives rise to neutrophils and macrophages and represents a promising system to derive new regulatory mechanisms for myeloid fate decision in vertebrates. Here we present an in vivo study of cell fate specification during zebrafish embryonic myelopoiesis through characterization of the embryos with altered Pu.1, Runx1 activity alone, or their combinations. Genetic analysis shows that low and high Pu.1 activities determine embryonic neutrophilic granulocyte and macrophage fate, respectively. Inactivation and overexpression of Runx1 in zebrafish uncover Runx1 as a key embryonic myeloid fate determinant that favors neutrophil over macrophage fate. Runx1 is induced by high Pu.1 level and in turn transrepresses pu.1 expression, thus constituting a negative feedback loop that fashions a favorable Pu.1 level required for balanced fate commitment to neutrophils versus macrophages. Our findings define a Pu.1-Runx1 regulatory loop that governs the equilibrium between distinct myeloid fates by assuring an appropriate Pu.1 dosage.

scholarly journals Regulatory network control of blood stem cells

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2614-2620 ◽  
Author(s):  
Berthold Göttgens
Keyword(s):  
Decision Making ◽  
Stem Cells ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Types ◽  
Network Control ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Fate Decision ◽  
Underlying Mechanisms

Abstract Hematopoietic stem cells (HSCs) are characterized by their ability to execute a wide range of cell fate choices, including self-renewal, quiescence, and differentiation into the many different mature blood lineages. Cell fate decision making in HSCs, as indeed in other cell types, is driven by the interplay of external stimuli and intracellular regulatory programs. Given the pivotal nature of HSC decision making for both normal and aberrant hematopoiesis, substantial research efforts have been invested over the last few decades into deciphering some of the underlying mechanisms. Central to the intracellular decision making processes are transcription factor proteins and their interactions within gene regulatory networks. More than 50 transcription factors have been shown to affect the functionality of HSCs. However, much remains to be learned about the way in which individual factors are connected within wider regulatory networks, and how the topology of HSC regulatory networks might affect HSC function. Nevertheless, important progress has been made in recent years, and new emerging technologies suggest that the pace of progress is likely to accelerate. This review will introduce key concepts, provide an integrated view of selected recent studies, and conclude with an outlook on possible future directions for this field.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Mesodermal Cell ◽  
Cell Lineages ◽  
Current Review ◽  
Differentiation Factors ◽  
The Relationship ◽  
Msc Differentiation

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

scholarly journals Structural and Functional Remodeling of Mitochondria in Cardiac Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4167
Author(s):  
Xiaonan Sun ◽  
Jalen Alford ◽  
Hongyu Qiu
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Therapeutic Potential ◽  
Research Direction ◽  
Future Research ◽  
Cardiac Diseases ◽  
Functional Remodeling ◽  
Underlying Mechanisms ◽  
Mitochondrial Remodeling ◽  
Normal Cellular Function

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

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