Proteomics of human embryonic stem cells

Hughes, Chris; Nuhn, A; Postovit, Lynne-Marie; Lajoie, Gilles

doi:10.1002/pmic.201000407

Cited by 23 publications

(15 citation statements)

References 129 publications

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“…Membrane proteomic analyses also suggest that BAP31 may be expressed on the surface of hESCs and human embryonal carcinoma cells . Based on the above membrane proteome analyses, it was suggested that BAP31 is likely to be a possible cell surface marker for undifferentiated hESCs . In this study, we demonstrate for the first time that BAP31 is a novel cell surface marker for undifferentiated hESCs.…”

Section: Discussionsupporting

confidence: 52%

B-Cell Receptor-Associated Protein 31 Regulates Human Embryonic Stem Cell Adhesion, Stemness, and Survival via Control of Epithelial Cell Adhesion Molecule

et al. 2014

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B-Cell receptor-associated protein 31 (BAP31) regulates the export of secreted membrane proteins from the endoplasmic reticulum (ER) to the downstream secretory pathway. Previously, we generated a monoclonal antibody 297-D4 against the surface molecule on undifferentiated human embryonic stem cells (hESCs). Here, we found that 297-D4 antigen was localized to pluripotent hESCs and downregulated during early differentiation of hESCs and identified that the antigen target of 297-D4 was BAP31 on the hESC-surface. To investigate the functional role of BAP31 in hESCs, BAP31 expression was knocked down by small interfering RNA. BAP31 depletion impaired hESC self-renewal and pluripotency and drove hESC differentiation into multicell lineages. BAP31 depletion hindered hESC proliferation by arresting cell cycle at G0/G1 phase and inducing caspase-independent cell death. Interestingly, BAP31 depletion reduced hESC adhesion to extracellular matrix (ECM). Analysis of cell surface molecules showed decreased expression of epithelial cell adhesion molecule (EpCAM) in BAP31-depleted hESCs, while ectopic expression of BAP31 elevated the expression of EpCAM. EpCAM depletion also reduced hESC adhesion to ECM, arrested cell cycle at G0/G1 phase and induced cell death, producing similar effects to those of BAP31 depletion. BAP31 and EpCAM were physically associated and colocalized at the ER and cell surface. Both BAP31 and EpCAM depletion decreased cyclin D1 and E expression and suppressed PI3K/Akt signaling, suggesting that BAP31 regulates hESC stemness and survival via control of EpCAM expression. These findings provide, for the first time, mechanistic insights into how BAP31 regulates hESC stemness and survival via control of EpCAM expression.

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Section: Discussionsupporting

confidence: 52%

B-Cell Receptor-Associated Protein 31 Regulates Human Embryonic Stem Cell Adhesion, Stemness, and Survival via Control of Epithelial Cell Adhesion Molecule

et al. 2014

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“…Given that the basement membrane is the first extracellular matrix (ECM) produced in the developing embryo, it was quickly identified as an important factor for modulating stem cell behavior [23], that plays multiple roles in the stem cell niche. It is perhaps not surprising then that BME is the gold standard for the maintenance of a wide array of human embryonic stem cell (hESC) lines, as it contains all of the proteins that have been shown to promote hESC growth when used individually [24]. …”

Section: Discussionmentioning

confidence: 99%

Basement Membrane-Rich Organoids with Functional Human Blood Vessels Are Permissive Niches for Human Breast Cancer Metastasis

et al. 2013

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Metastasic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention.

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“…Accordingly, many researchers investigated the role of EVs released by iPSCs in tissue regeneration. Several proteomic analyses have identified cytokines, chaperones, signaling molecules, plasma membrane proteins, isolated from human pluripotent stem cells [194,195], and it is reasonable to hypothesize that iPSC-EVs contain many kinds of these proteins. Therefore, many researchers shifted their attention to the EVs released by transplanted cells.…”

Section: Induced Pluripotent Stem Cell Derived Evs In Regenerative Mementioning

confidence: 99%

Extracellular Vesicles: The New Frontier of Stem Cell Regenerative Medicine?

Barreca¹,

Geraci²

2020

Preprint

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Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

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Proteomics of human embryonic stem cells

Cited by 23 publications

References 129 publications

B-Cell Receptor-Associated Protein 31 Regulates Human Embryonic Stem Cell Adhesion, Stemness, and Survival via Control of Epithelial Cell Adhesion Molecule

B-Cell Receptor-Associated Protein 31 Regulates Human Embryonic Stem Cell Adhesion, Stemness, and Survival via Control of Epithelial Cell Adhesion Molecule

Basement Membrane-Rich Organoids with Functional Human Blood Vessels Are Permissive Niches for Human Breast Cancer Metastasis

Extracellular Vesicles: The New Frontier of Stem Cell Regenerative Medicine?

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