Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot, Marie; Demarco, Rafael Sênos; Jones, D. Leanne

doi:10.3389/fcell.2020.00115

Cited by 52 publications

(57 citation statements)

References 138 publications

(202 reference statements)

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“…At 42 dpa, most enriched pathways are related to cell energetic metabolism, as the catabolism of branched-chain fatty acids (BCFA) and branched-chain amino acids (BCAA), suggesting an increased mitochondrial activity ( Figure 11A) (Neinast et al, 2019;Clémot et al, 2020). Active lipolysis of phospholipids and triacylglycerols, reflected in the low abundance of several BCFA species included lysoPC and lysoPE, explain the promotion of ketone body metabolism and the Krebs cycle (TCA) (Grabacka et al, 2016).…”

Section: Metabolic Reprogramming During Forelimb Regenerationmentioning

confidence: 99%

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

Varela-Rodríguez

Abella-Quintana

Espinal-Centeno

et al. 2020

Front. Cell Dev. Biol.

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The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.

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“…5 A,B, Tables S3 and S4). Increased lipid remodeling and cholesterol biosynthesis has been implicated in enhanced stem cell maintenance, proliferation, and tumorigenesis both in vivo and in organoids 35 , 36 . In our studies, lipid biosynthesis upregulation likely reflects the increased stem cell composition of organoids relative to stromal rich PDXs.…”

Section: Resultsmentioning

confidence: 99%

A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture

Cai

García

Liu

et al. 2021

Sci Rep

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Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies.

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“…Lipid metabolism plays a pivotal role in stem cells physiopathology [ 108 , 109 , 110 ]. However, at the moment the number of studies about the lipidome of MSCs is limited, and mainly focused on variations in lipid composition during stem cell proliferation and differentiation [ 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ] ( Figure 2 ).…”

Section: Bioactive Lipids In Mscsmentioning

confidence: 99%

Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation

Casati

Giannasi

Niada

et al. 2021

IJMS

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Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario. Indeed, MSCs are a heterogenous population of multipotent cells that have attracted much attention for their potential in regulating inflammation, immunomodulatory capabilities, and reparative roles. The lipidomics of the inflammatory disease osteoarthritis (OA) and the influence of MSCs-derived lipids have also been addressed.

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“…More and more reports have been released regarding the lipid profile of MSCs recently, and the role of lipoproteins in altering MSC functions and properties, including their proliferation capacity, immune-modulatory functions, immunomodulatory regulation, and the differentiation potential of multiple lineages [ 47 , 48 ], although most of these investigations have focused on the effect of lipids in regulating MSCs’ adipogenic differentiation capability. However, uncertainty persists regarding the relevance of MSC differentiation through cardiomyogenesis and vasculargenesis.…”

Section: The Regulatory Effect Of Lipids On Mscs In Cardiac Regenementioning

confidence: 99%

Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration

Lin

Kang

Feng

et al. 2020

IJMS

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Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation.

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“…Lipidomics is one of the most recent, rapidly developing and promising approaches [ 13 ]. Lipidomics studies the state of the lipid molecular phenotype, reflecting the functional “landscape” of lipid activity in cells and tissues [ 14 ]. For this reason, clinical lipidomics offers the possibility of elucidating the strategic roles of lipids in disease and the immune system [ 15 ], identifying biomarkers and developing new therapeutics [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome

et al. 2020

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Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two patients, including 21 patients with sepsis and 21 patients with SIRS, were involved in the study. Liquid chromatography coupled to mass spectrometry and multivariate statistical methods were used to determine lipids present in patient plasma. The obtained lipid signatures revealed 355 features for the negative ion mode and 297 for the positive ion mode, which were relevant for differential diagnosis of sepsis and SIRS. These lipids were also tested as prognosis predictors. Lastly, L-octanoylcarnitine was found to be the most promising lipid signature for both the diagnosis and prognosis of critically ill patients, with accuracies of 75% for both purposes. In short, we presented the determination of lipid signatures as a potential tool for differential diagnosis of sepsis and SIRS and prognosis of these patients.

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Lipid Mediated Regulation of Adult Stem Cell Behavior

Cited by 52 publications

References 138 publications

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture

Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation

Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome

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