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  1. Article ; Online: Suspension-Induced Stem Cell Transition: A Non-Transgenic Method to Generate Adult Stem Cells from Mouse and Human Somatic Cells.

    Yeganeh, Behzad / Yeganeh, Azadeh / Malone, Kyle / Beug, Shawn T / Jankov, Robert P

    Cells

    2023  Volume 12, Issue 20

    Abstract: Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts, grown in suspension, change from the elongated and ...

    Abstract Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts, grown in suspension, change from the elongated and flattened morphology observed under standard adherent culture conditions of generating rounded cells with large nuclei and scant cytoplasm and expressing the mesenchymal stem cell (MSC) marker (Sca1; Ly6A) within 24 h. Based on this initial observation, we describe here a suspension culture method that, irrespective of the lineage used, mouse fibroblast or primary human somatic cells (fibroblasts, hepatocytes and keratinocytes), is capable of generating a high yield of cells in spheroid form which display the expression of ASC surface markers, circumventing the anoikis which often occurs at this stage. Moreover, mouse fibroblast-derived spheroids can be differentiated into adipogenic and osteogenic lineages. An analysis of single-cell RNA sequence data in mouse fibroblasts identified eight distinct cell clusters with one in particular comprising approximately 10% of the cells showing high levels of proliferative capacity expressing high levels of genes related to MSCs and self-renewal as well as the extracellular matrix (ECM). We believe the rapid, high-yield generation of proliferative, multi-potent ASC-like cells via the process we term suspension-induced stem cell transition (SIST) could have significant implications for regenerative medicine.
    MeSH term(s) Adult ; Humans ; Animals ; Mice ; Stem Cells ; Cell Differentiation ; Mesenchymal Stem Cells/metabolism ; Adult Stem Cells ; Animals, Genetically Modified
    Language English
    Publishing date 2023-10-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12202508
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release.

    Horbay, Rostyslav / Hamraghani, Ali / Ermini, Leonardo / Holcik, Sophie / Beug, Shawn T / Yeganeh, Behzad

    International journal of molecular sciences

    2022  Volume 23, Issue 23

    Abstract: Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations ... ...

    Abstract Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations of EV biogenesis, sorting, release and uptake is the basis of a number of disorders. In this review, we summarize recent advances of the complex roles of the sphingolipid ceramide and lysosomes in the journey of EV biogenesis to uptake.
    Language English
    Publishing date 2022-12-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms232315317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Autophagy in Tumor Immunity and Viral-Based Immunotherapeutic Approaches in Cancer.

    Zahedi-Amiri, Ali / Malone, Kyle / Beug, Shawn T / Alain, Tommy / Yeganeh, Behzad

    Cells

    2021  Volume 10, Issue 10

    Abstract: Autophagy is a fundamental catabolic process essential for the maintenance of cellular and tissue homeostasis, as well as directly contributing to the control of invading pathogens. Unsurprisingly, this process becomes critical in supporting cellular ... ...

    Abstract Autophagy is a fundamental catabolic process essential for the maintenance of cellular and tissue homeostasis, as well as directly contributing to the control of invading pathogens. Unsurprisingly, this process becomes critical in supporting cellular dysregulation that occurs in cancer, particularly the tumor microenvironments and their immune cell infiltration, ultimately playing a role in responses to cancer therapies. Therefore, understanding "cancer autophagy" could help turn this cellular waste-management service into a powerful ally for specific therapeutics. For instance, numerous regulatory mechanisms of the autophagic machinery can contribute to the anti-tumor properties of oncolytic viruses (OVs), which comprise a diverse class of replication-competent viruses with potential as cancer immunotherapeutics. In that context, autophagy can either: promote OV anti-tumor effects by enhancing infectivity and replication, mediating oncolysis, and inducing autophagic and immunogenic cell death; or reduce OV cytotoxicity by providing survival cues to tumor cells. These properties make the catabolic process of autophagy an attractive target for therapeutic combinations looking to enhance the efficacy of OVs. In this article, we review the complicated role of autophagy in cancer initiation and development, its effect on modulating OVs and immunity, and we discuss recent progress and opportunities/challenges in targeting autophagy to enhance oncolytic viral immunotherapy.
    MeSH term(s) Autophagy ; Carcinogenesis/pathology ; Humans ; Immunogenic Cell Death ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; Neoplasms/virology ; Oncolytic Viruses/physiology
    Language English
    Publishing date 2021-10-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10102672
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Explant Culture for Studying Lung Development.

    Yeganeh, Behzad / Bilodeau, Claudia / Post, Martin

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1752, Page(s) 81–90

    Abstract: Lung development is a complex process that requires the input of various signaling pathways to coordinate the specification and differentiation of multiple cell types. Ex vivo culture of the lung is a very useful technique that represents an attractive ... ...

    Abstract Lung development is a complex process that requires the input of various signaling pathways to coordinate the specification and differentiation of multiple cell types. Ex vivo culture of the lung is a very useful technique that represents an attractive model for investigating many different processes critical to lung development, function, and disease pathology. Ex vivo cultured lungs remain comparable to the in vivo lung both in structure and function, which makes them more suitable than cell cultures for physiological studies. Lung explant cultures offer several significant advantages for studies of morphogenetic events that guide lung development including budding, branching, and fusion. It also maintains the native physiological interactions between cells in the developing lung, enabling investigations of the direct and indirect signaling taking place between tissues and cells throughout the developmental process. Studying temporal and spatial control of gene expression by transcriptional factors using different reporters to understand their regulatory function at different moments of development is another valuable advantage of lung explants culture.
    MeSH term(s) Animals ; Female ; Lung/embryology ; Lung/growth & development ; Mice ; Organ Culture Techniques/methods ; Pregnancy
    Language English
    Publishing date 2018-03-21
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7714-7_8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Thrombospondin-1 Plays a Major Pathogenic Role in Experimental and Human Bronchopulmonary Dysplasia.

    Ruschkowski, Brittany Ann / Esmaeil, Yousef / Daniel, Kate / Gaudet, Chantal / Yeganeh, Behzad / Grynspan, David / Jankov, Robert P

    American journal of respiratory and critical care medicine

    2022  Volume 205, Issue 6, Page(s) 685–699

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Bleomycin ; Bronchopulmonary Dysplasia ; Humans ; Infant, Newborn ; Infant, Premature ; Leucine ; Lung Injury ; Rats ; Thrombospondin 1/metabolism ; Thrombospondin 1/pharmacology ; Transforming Growth Factor beta1/metabolism
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; SPZ1 protein, human ; Thrombospondin 1 ; Transforming Growth Factor beta1 ; Bleomycin (11056-06-7) ; Leucine (GMW67QNF9C)
    Language English
    Publishing date 2022-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202104-1021OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Editorial (Thematic Issue: New Insights into a Classical Pathway: Key Roles of the Mevalonate Cascade in Different Diseases (Part I)).

    Ghavami, Saeid / Kenyon, Nicholas J / Yeganeh, Behzad / Zeki, Amir A

    Current molecular pharmacology

    2018  Volume 10, Issue 1, Page(s) 3–5

    MeSH term(s) Cholesterol/metabolism ; Disease ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Mevalonic Acid/metabolism
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Cholesterol (97C5T2UQ7J) ; Mevalonic Acid (S5UOB36OCZ)
    Language English
    Publishing date 2018-08-02
    Publishing country United Arab Emirates
    Document type Editorial ; Introductory Journal Article
    ISSN 1874-4702
    ISSN (online) 1874-4702
    DOI 10.2174/1874467209999160114145952
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Autophagy is required for lung development and morphogenesis.

    Yeganeh, Behzad / Lee, Joyce / Ermini, Leonardo / Lok, Irene / Ackerley, Cameron / Post, Martin

    The Journal of clinical investigation

    2019  Volume 129, Issue 7, Page(s) 2904–2919

    Abstract: Bronchopulmonary dysplasia (BPD) remains a major respiratory illness in extremely premature infants. The biological mechanisms leading to BPD are not fully understood, although an arrest in lung development has been implicated. The current study aimed to ...

    Abstract Bronchopulmonary dysplasia (BPD) remains a major respiratory illness in extremely premature infants. The biological mechanisms leading to BPD are not fully understood, although an arrest in lung development has been implicated. The current study aimed to investigate the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation. We found 2 windows of epithelial autophagy activation in the developing mouse lung, both resulting from AMPK activation. Inhibition of AMPK-mediated autophagy led to reduced lung branching in vitro. Conditional deletion of beclin 1 (Becn1) in mouse lung epithelial cells (Becn1Epi-KO), either at early (E10.5) or late (E16.5) gestation, resulted in lethal respiratory distress at birth or shortly after. E10.5 Becn1Epi-KO lungs displayed reduced airway branching and sacculi formation accompanied by impaired vascularization, excessive epithelial cell death, reduced mesenchymal thinning of the interstitial walls, and delayed epithelial maturation. E16.5 Becn1Epi-KO lungs had reduced terminal air sac formation and vascularization and delayed distal epithelial differentiation, a pathology similar to that seen in infants with BPD. Taken together, our findings demonstrate that intrinsic autophagy is an important regulator of lung development and morphogenesis and may contribute to the BPD phenotype when impaired.
    MeSH term(s) Animals ; Autophagic Cell Death ; Beclin-1/genetics ; Beclin-1/metabolism ; Bronchopulmonary Dysplasia/embryology ; Bronchopulmonary Dysplasia/genetics ; Bronchopulmonary Dysplasia/pathology ; Lung/embryology ; Lung/pathology ; Mice ; Mice, Knockout ; Organogenesis
    Chemical Substances Beclin-1 ; Becn1 protein, mouse
    Language English
    Publishing date 2019-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI127307
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Editorial: New Insights into a Classical Pathway: Key Roles of the Mevalonate Cascade in Different Diseases (Part II).

    Zeki, Amir A / Yeganeh, Behzad / Kenyon, Nicholas J / Ghavami, Saeid

    Current molecular pharmacology

    2017  Volume 10, Issue 2, Page(s) 74–76

    MeSH term(s) Disease ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Mevalonic Acid/metabolism
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Mevalonic Acid (S5UOB36OCZ)
    Language English
    Publishing date 2017-04-21
    Publishing country United Arab Emirates
    Document type Editorial ; Introductory Journal Article
    ISSN 1874-4702
    ISSN (online) 1874-4702
    DOI 10.2174/187446721002170301204357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Sphingolipids as cell fate regulators in lung development and disease.

    Lee, Joyce / Yeganeh, Behzad / Ermini, Leonardo / Post, Martin

    Apoptosis : an international journal on programmed cell death

    2015  Volume 20, Issue 5, Page(s) 740–757

    Abstract: Sphingolipids are a diverse class of signaling molecules implicated in many important aspects of cellular biology, including growth, differentiation, apoptosis, and autophagy. Autophagy and apoptosis are fundamental physiological processes essential for ... ...

    Abstract Sphingolipids are a diverse class of signaling molecules implicated in many important aspects of cellular biology, including growth, differentiation, apoptosis, and autophagy. Autophagy and apoptosis are fundamental physiological processes essential for the maintenance of cellular and tissue homeostasis. There is great interest into the investigation of sphingolipids and their roles in regulating these key physiological processes as well as the manifestation of several disease states. With what is known to date, the entire scope of sphingolipid signaling is too broad, and a single review would hardly scratch the surface. Therefore, this review attempts to highlight the significance of sphingolipids in determining cell fate (e.g. apoptosis, autophagy, cell survival) in the context of the healthy lung, as well as various respiratory diseases including acute lung injury, acute respiratory distress syndrome, bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, emphysema, and cystic fibrosis. We present an overview of the latest findings related to sphingolipids and their metabolites, provide a short introduction to autophagy and apoptosis, and then briefly highlight the regulatory roles of sphingolipid metabolites in switching between cell survival and cell death. Finally, we describe functions of sphingolipids in autophagy and apoptosis in lung homeostasis, especially in the context of the aforementioned diseases.
    MeSH term(s) Animals ; Apoptosis ; Autophagy ; Cell Survival ; Homeostasis ; Humans ; Lung/growth & development ; Lung/metabolism ; Lung/pathology ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Signal Transduction ; Sphingolipids/physiology
    Chemical Substances Sphingolipids
    Language English
    Publishing date 2015-01-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1452360-7
    ISSN 1573-675X ; 1360-8185
    ISSN (online) 1573-675X
    ISSN 1360-8185
    DOI 10.1007/s10495-015-1112-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Acid Sphingomyelinase Inhibition Attenuates Cell Death in Mechanically Ventilated Newborn Rat Lung.

    Yeganeh, Behzad / Lee, Joyce / Bilodeau, Claudia / Lok, Irene / Ermini, Leonardo / Ackerley, Cameron / Caniggia, Isabella / Tibboel, Jeroen / Kroon, Andre / Post, Martin

    American journal of respiratory and critical care medicine

    2018  Volume 199, Issue 6, Page(s) 760–772

    Abstract: Rationale: Premature infants subjected to mechanical ventilation (MV) are prone to lung injury that may result in bronchopulmonary dysplasia. MV causes epithelial cell death and halts alveolar development. The exact mechanism of MV-induced epithelial ... ...

    Abstract Rationale: Premature infants subjected to mechanical ventilation (MV) are prone to lung injury that may result in bronchopulmonary dysplasia. MV causes epithelial cell death and halts alveolar development. The exact mechanism of MV-induced epithelial cell death is unknown.
    Objectives: To determine the contribution of autophagy to MV-induced epithelial cell death in newborn rat lungs.
    Methods: Newborn rat lungs and fetal rat lung epithelial (FRLE) cells were exposed to MV and cyclic stretch, respectively, and were then analyzed by immunoblotting and mass spectrometry for autophagy, apoptosis, and bioactive sphingolipids.
    Measurements and main results: Both MV and stretch first induce autophagy (ATG 5-12 [autophagy related 5-12] and LC3B-II [microtubule-associated proteins 1A/1B light chain 3B-II] formation) followed by extrinsic apoptosis (cleaved CASP8/3 [caspase-8/3] and PARP [poly(ADP-ribose) polymerase] formation). Stretch-induced apoptosis was attenuated by inhibiting autophagy. Coimmunoprecipitation revealed that stretch promoted an interaction between LC3B and the FAS (first apoptosis signal) cell death receptor in FRLE cells. Ceramide levels, in particular C16 ceramide, were rapidly elevated in response to ventilation and stretch, and C16 ceramide treatment of FRLE cells induced autophagy and apoptosis in a temporal pattern similar to that seen with MV and stretch. SMPD1 (sphingomyelin phosphodiesterase 1) was activated by ventilation and stretch, and its inhibition prevented ceramide production, LC3B-II formation, LC3B/first apoptosis signal interaction, caspase-3 activation, and, ultimately, FLRE cell death. SMPD1 inhibition also attenuated ventilation-induced autophagy and apoptosis in newborn rats.
    Conclusions: Ventilation-induced ceramides promote autophagy-mediated cell death, and identifies SMPD1 as a potential therapeutic target for the treatment of ventilation-induced lung injury in newborns.
    MeSH term(s) Animals ; Animals, Newborn ; Cell Death/drug effects ; Epithelial Cells/drug effects ; Humans ; Infant, Newborn/physiology ; Lung/metabolism ; Models, Animal ; Rats ; Respiration, Artificial ; Sphingomyelin Phosphodiesterase/metabolism
    Chemical Substances Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
    Language English
    Publishing date 2018-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.201803-0583OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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