Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells

Vassalli, Giuseppe

doi:10.1155/2019/3904645

Cited by 240 publications

(208 citation statements)

References 189 publications

(241 reference statements)

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“…In this particular case, cysteine stopped the ROS-induced monocyte-ECs differentiation, as it prevented the expression of vWF and impaired the route of monocytes to EC-like differentiation ( Figure 2C). EPCs are characterized by having active ALDH and a decrease in their expression and activity is correlated with a differentiation status of EPCs to ECs [36,37]. In a model of ischemia, decreased expression of ALDH was pointed out as a good strategy to induce rapid neovascularization and subsequent regeneration of ischemic tissues [69].…”

Section: Discussionmentioning

confidence: 99%

“…Aldehyde dehydrogenase (ALDH) is used as a marker for populations enriched in stem and progenitor cells and a decrease in ALDH expression and activity is correlated with a differentiation status of EPCs to ECs [36,37]. Hence, the impact of ALDH inhibition by disulfiram [38] was evaluated in the monocyte-endothelial differentiation.…”

Section: Reactive Oxygen Species (Ros) Promote Monocytes Differentiatmentioning

confidence: 99%

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Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

Lopes‐Coelho

Silva

Gouveia-Fernandes

et al. 2020

Cells

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Bone marrow contains endothelial progenitor cells (EPCs) that, upon pro-angiogenic stimuli, migrate and differentiate into endothelial cells (ECs) and contribute to re-endothelialization and neo-vascularization. There are currently no reliable markers to characterize EPCs, leading to their inaccurate identification. In the past, we showed that, in a panel of tumors, some cells on the vessel wall co-expressed CD14 (monocytic marker) and CD31 (EC marker), indicating a putative differentiation route of monocytes into ECs. Herein, we disclosed monocytes as potential EPCs, using in vitro and in vivo models, and also addressed the cancer context. Monocytes acquired the capacity to express ECs markers and were able to be incorporated into blood vessels, contributing to cancer progression, by being incorporated in tumor neo-vasculature. Reactive oxygen species (ROS) push monocytes to EC differentiation, and this phenotype is reverted by cysteine (a scavenger and precursor of glutathione), which indicates that angiogenesis is controlled by the interplay between the oxidative stress and the scavenging capacity of the tumor microenvironment.Over the last decade, different studies reported EPCs as essential in restoring injured vessels. EPCs belong to a subset of cells, arising from hematopoietic stem cells in bone marrow; upon pro-angiogenic stimuli, they proliferate, migrate, and differentiate into endothelial cells (ECs) [4][5][6]. Some reports addressing EPCs and disease, such as systemic sclerosis, showed contradictory and discrepant results about EPCs mobilization and differentiation; in part, because there is a lack of a precise panel of cell surface markers used for the characterization of this subset of cells [4][5][6][7][8][9][10]. In mouse embryonic vascular endothelium, erythro-myeloid progenitors (EMPs) can differentiate into ECs [11] and in a mouse model of carotid injury, monocytes (CD14 + cells) are capable of improving re-endothelialization [12]. In vivo and in vitro targeting of Tie2-monocytes decreases angiogenesis by abrogating EC proliferation [13][14][15] and an in vivo CCR2 (chemokine (C-C motif) receptor 2) knockout impairs monocytes recruitment and VEGFA (also named VEGF, vascular endothelial growth factor) expression, accompanied by a reduction in the angiogenesis rate [16]. The release of cytokines and pro-angiogenic factors (e.g., VEGFA, VEGFC, and VEGFD, TNFα (tumor necrosis factor α), IL-8 (interleukin-8), and FGF-2 (fibroblast growth factor-2), and extracellular matrix (ECM) modifying proteins (e.g., metalloproteinase-9 (MMP-9)) by macrophages enhances the tissue's ability to support capillary sprouting and vascular density [17,18]. The precise mechanism by which monocytes influence angiogenesis in tissue development, homeostasis, and diseases is not fully understood. However, different studies, have shown that under in vitro pro-angiogenic pressure, blood mononuclear cells can acquire endothelial markers and morphology [19][20][21]. In addition, in a previous study, we showed that some ECs sim...

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Section: Discussionmentioning

confidence: 99%

Section: Reactive Oxygen Species (Ros) Promote Monocytes Differentiatmentioning

confidence: 99%

Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

Lopes‐Coelho

Silva

Gouveia-Fernandes

et al. 2020

Cells

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“…The ALDH1A3 gene product is the aldehyde dehydrogenase 1A3 [46]. This enzyme is involved in production of retinoic acid, particularly through oxidizing all-trans-retinal [46,47]. Therefore, its deficiency results in impairment of eye formation and functions.…”

Section: Discussionmentioning

confidence: 99%

Genetic Base of Behavioral Disorders in Mucopolysaccharidoses: Transcriptomic Studies

Pierzynowska

Gaffke

Podlacha

et al. 2020

IJMS

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Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases caused by mutations leading to defective degradation of glycosaminoglycans (GAGs) and their accumulation in cells. Among 11 known types and subtypes of MPS, neuronopathy occurs in seven (MPS I, II, IIIA, IIIB, IIIC, IIID, VII). Brain dysfunctions, occurring in these seven types/subtypes include various behavioral disorders. Intriguingly, behavioral symptoms are significantly different between patients suffering from various MPS types. Molecular base of such differences remains unknown. Here, we asked if expression of genes considered as connected to behavior (based on Gene Ontology, GO terms) is changed in MPS. Using cell lines of all MPS types, we have performed transcriptomic (RNA-seq) studies and assessed expression of genes involved in behavior. We found significant differences between MPS types in this regard, with the most severe changes in MPS IIIA (the type considered as the behaviorally most severely affected), while the lowest changes in MPS IVA and MPS VI (types in which little or no behavioral disorders are known). Intriguingly, relatively severe changes were found also in MPS IVB (in which, despite no behavioral disorder noted, the same gene is mutated as in GM1 gangliosidosis, a severe neurodegenerative disease) and MPS IX (in which only a few patients were described to date, thus, behavioral problems are not well recognized). More detailed analyses of expression of certain genes allowed us to propose an association of specific changes in the levels of transcripts in specific MPS types to certain behavioral disorders observed in patients. Therefore, this work provides a principle for further studies on the molecular mechanism of behavioral changes occurring in MPS patients.

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“…CD24 -/CD44 + cells) [26] ( Figures 3A and 3B). Overexpressing GRP78 also induced the expression of aldehyde dehydrogenase 1 (ALDH1A), a marker associated with stemness and cancer [27] (Supplementary Figure S4).…”

Section: Resultsmentioning

confidence: 99%

GRP78 promotes stemness in normal and neoplastic cells

Conner

Lager

Guldner

et al. 2019

Preprint

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Reliable approaches to identify stem cell mechanisms that mediate aggressive cancer could have great therapeutic value, based on the growing evidence of embryonic signatures in metastatic cancers. However, how to best identify and target stem-like mechanisms aberrantly acquired by cancer cells has been challenging. We harnessed the power of reprogramming to examine GRP78, a chaperone protein generally restricted to the endoplasmic reticulum in normal tissues, but which is expressed on the cell surface of human embryonic stem cells and many cancer types. We have discovered that (1) cell surface GRP78 (sGRP78) is expressed on iPSCs and is important in reprogramming, (2) sGRP78 promotes cellular functions in both pluripotent and breast cancer cells (3) overexpression of GRP78 in breast cancer cells leads to an induction of a CD24 -/CD44 + tumor initiating cell (TIC) population (4) sGRP78 + breast cancer cells are enriched for stemness genes and appear to be a subset of TICs (5) sGRP78 + breast cancer cells show an enhanced ability to seed metastatic organ sites in vivo. These collective findings show that GRP78 has important functions in regulating both pluripotency and oncogenesis, and suggest that sGRP78 marks a stem-like population in breast cancer cells that has increased metastatic potential in vivo.

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Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells

Cited by 240 publications

References 189 publications

Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

Genetic Base of Behavioral Disorders in Mucopolysaccharidoses: Transcriptomic Studies

GRP78 promotes stemness in normal and neoplastic cells

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