المؤلفون: Christodoulou, Constantina, Spencer, Joel A, Yeh, Shu-Chi A, Turcotte, Raphaël, Kokkaliaris, Konstantinos D, Panero, Riccardo, Ramos, Azucena, Guo, Guoji, Seyedhassantehrani, Negar, Esipova, Tatiana V, Vinogradov, Sergei A, Rudzinskas, Sarah, Zhang, Yi, Perkins, Archibald S, Orkin, Stuart H, Calogero, Raffaele A, Schroeder, Timm, Lin, Charles P, Camargo, Fernando D

المصدر: Nature. 578(7794)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Transplantation, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Animals, Bone Remodeling, Cell Movement, Cell Proliferation, Cell Survival, Female, Genes, Reporter, Hematopoietic Stem Cells, Hypoxia, MDS1 and EVI1 Complex Locus Protein, Male, Mice, Molecular Imaging, Oxygen, Skull, fms-Like Tyrosine Kinase 3, General Science & Technology

الوصف: The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow3-5. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1n90468cTest

المؤلفون: Cowan, Cameron S., Renner, Magdalena, De Gennaro, Martina, Gross Scherf, Brigitte, Goldblum, David, Hou, Yanyan, Munz, Martin, Rodrigues, Tiago M., Krol, Jacek, Szikra, Tamas, Cuttat, Rachel, Waldt, Annick, Papasaikas, Panagiotis, Diggelmann, Roland, Patino Alvarez, Claudia P., Galliker, Patricia, Spirig, Stefan E., Pavlinic, Dinko, Gerber-Hollbach, Nadine, Schuierer, Sven, Srdanovic, Aldin, Balogh, Marton, Panero, Riccardo, Kusnyerik, Ákos, Szabo, Arnold, Stadler, Michael B., Orgül, Selim, Picelli, Simone, Hasler, Pascal W., Hierlemann, Andreas, id_orcid:0 000-0002-3838-2468, Scholl, Hendrik P.N., Roma, Guglielmo, Nigsch, Florian, Roska, Botond

المصدر: Cell, 182 (6)

الوصف: Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable “developed” state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas. ; ISSN:0092-8674 ; ISSN:1097-4172

وصف الملف: application/application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/wos/000571443300022; info:eu-repo/grantAgreement/SNF/Sinergia/141801; http://hdl.handle.net/20.500.11850/441335Test

الإتاحة: https://doi.org/20.500.11850/441335Test
https://doi.org/10.3929/ethz-b-000441335Test
https://doi.org/10.1016/j.cell.2020.08.013Test
https://hdl.handle.net/20.500.11850/441335Test

المؤلفون: Cheung, Priscilla, Xiol, Jordi, Dill, Michael T., Yuan, Wei-Chien, Panero, Riccardo, Roper, Jatin, Osorio, Fernando G., Maglic, Dejan, Li, Qi, Gurung, Basanta, Calogero, Raffaele A., Yilmaz, Ömer H., Mao, Junhao, Camargo, Fernando D.

المساهمون: Human Frontier Science Program, National Institutes of Health

المصدر: Cell Stem Cell ; volume 27, issue 4, page 590-604.e9 ; ISSN 1934-5909

الإتاحة: https://doi.org/10.1016/j.stem.2020.07.003Test
https://api.elsevier.com/content/article/PII:S1934590920303416?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1934590920303416?httpAccept=text/plainTest

المؤلفون: Rodriguez-Fraticelli, Alejo E., Wolock, Samuel L., Weinreb, Caleb S., Panero, Riccardo, Patel, Sachin H., Jankovic, Maja, Sun, Jianlong, Calogero, Raffaele A., Klein, Allon M., Camargo, Fernando D.

المساهمون: Rodriguez-Fraticelli, Alejo E., Wolock, Samuel L., Weinreb, Caleb S., Panero, Riccardo, Patel, Sachin H., Jankovic, Maja, Sun, Jianlong, Calogero, Raffaele A., Klein, Allon M., Camargo, Fernando D.

الوصف: Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29323290; info:eu-repo/semantics/altIdentifier/wos/WOS:000419794800038; volume:553; issue:7687; firstpage:212; lastpage:216; numberofpages:5; journal:NATURE; http://hdl.handle.net/2318/1656179Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85040442896; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884107Test/

الإتاحة: https://doi.org/10.1038/nature25168Test
http://hdl.handle.net/2318/1656179Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884107Test/

المؤلفون: BECCUTI, Marco, CORDERO, Francesca, ARIGONI, MADDALENA, PANERO, RICCARDO, AMPARORE, ELVIO GILBERTO, DONATELLI, Susanna, CALOGERO, Raffaele Adolfo

المساهمون: Beccuti, Marco, Cordero, Francesca, Arigoni, Maddalena, Panero, Riccardo, Amparore, Elvio G, Donatelli, Susanna, Calogero, Raffaele A.

الوصف: Short reads sequencing technology has been used for more than a decade now. However, the analysis of RNAseq and ChIPseq data is still computational demanding and the simple access to raw data does not guarantee results reproducibility between laboratories. To address these two aspects, we developed SeqBox, a cheap, efficient and reproducible RNAseq/ChIPseq hardware/software solution based on NUC6I7KYK mini-PC (an Intel consumer game computer with a fast processor and a high performance SSD disk), and Docker container platform. In SeqBox the analysis of RNAseq and ChIPseq data is supported by a friendly GUI. This allows access to fast and reproducible analysis also to scientists with/without scripting experience.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29069297; info:eu-repo/semantics/altIdentifier/wos/WOS:000426813500022; firstpage:1; lastpage:2; numberofpages:2; journal:BIOINFORMATICS; http://hdl.handle.net/2318/1650770Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85042943380

الإتاحة: https://doi.org/10.1093/bioinformatics/btx674Test
http://hdl.handle.net/2318/1650770Test

المؤلفون: Maglic, Dejan, Schlegelmilch, Karin, Dost, Antonella FM, Panero, Riccardo, Dill, Michael T, Calogero, Raffaele A, Camargo, Fernando D

المساهمون: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute

المصدر: The EMBO Journal ; volume 37, issue 17 ; ISSN 0261-4189 1460-2075

مصطلحات موضوعية: General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology, General Neuroscience

الإتاحة: https://doi.org/10.15252/embj.201798642Test

المؤلفون: Kulkarni, Neha, Alessandrì, Luca, Panero, Riccardo, Arigoni, Maddalena, Olivero, Martina, Ferrero, Giulio, Cordero, Francesca, Beccuti, Marco, Calogero, Raffaele A.

المصدر: BMC Bioinformatics ; volume 19, issue S10 ; ISSN 1471-2105

مصطلحات موضوعية: Applied Mathematics, Computer Science Applications, Molecular Biology, Biochemistry, Structural Biology

الإتاحة: https://doi.org/10.1186/s12859-018-2296-xTest

المؤلفون: Panero, Riccardo, Rinaldi, Antonio, Memoli, Domenico, Nassa, Giovanni, Ravo, Maria, Rizzo, Francesca, Tarallo, Roberta, Milanesi, Luciano, Weisz, Alessandro, Giurato, Giorgio

المصدر: Bioinformatics ; volume 33, issue 24, page 4050-4050 ; ISSN 1367-4803 1367-4811

مصطلحات موضوعية: Computational Mathematics, Computational Theory and Mathematics, Computer Science Applications, Molecular Biology, Biochemistry, Statistics and Probability

الإتاحة: https://doi.org/10.1093/bioinformatics/btx647Test
https://academic.oup.com/bioinformatics/article-pdf/33/24/4050/49041874/bioinformatics_33_24_4050.pdfTest

المؤلفون: Panero, Riccardo, Rinaldi, Antonio, Memoli, Domenico, Nassa, Giovanni, Ravo, Maria, Rizzo, Francesca, Tarallo, Roberta, Milanesi, Luciano, Weisz, Alessandro, Giurato, Giorgio

المساهمون: Bar-Joseph, Ziv

المصدر: Bioinformatics ; volume 33, issue 6, page 938-940 ; ISSN 1367-4803 1367-4811

مصطلحات موضوعية: Computational Mathematics, Computational Theory and Mathematics, Computer Science Applications, Molecular Biology, Biochemistry, Statistics and Probability

الوصف: Summary The interest in investigating the biological roles of small non-coding RNAs (sncRNAs) is increasing, due to the pleiotropic effects of these molecules exert in many biological contexts. While several methods and tools are available to study microRNAs (miRNAs), only few focus on novel classes of sncRNAs, in particular PIWI-interacting RNAs (piRNAs). To overcome these limitations, we implemented iSmaRT (integrative Small RNA Tool-kit), an automated pipeline to analyze smallRNA-Seq data. Availability and Implementation iSmaRT is a collection of bioinformatics tools and own algorithms, interconnected through a Graphical User Interface (GUI). In addition to performing comprehensive analyses on miRNAs, it implements specific computational modules to analyze piRNAs, predicting novel ones and identifying their RNA targets. A smallRNA-Seq dataset generated from brain samples of Huntington’s Disease patients was used here to illustrate iSmaRT performances, demonstrating how the pipeline can provide, in a rapid and user friendly way, a comprehensive analysis of different classes of sncRNAs. iSmaRT is freely available on the web at ftp://labmedmolge-1.unisa.it (User: iSmart - Password: password) Supplementary information Supplementary data are available at Bioinformatics online.

الإتاحة: https://doi.org/10.1093/bioinformatics/btw734Test
https://academic.oup.com/bioinformatics/article-pdf/33/6/938/49038221/bioinformatics_33_6_938.pdfTest

المؤلفون: Cowan, Cameron, Renner, Magdalena, De Gennaro, Martina, Gross-Scherf, Brigitte, Goldblum, David, Hou, Yanyan, Munz, Martin, Rodrigues, Tiago M., Krol, Jacek, Szikra, Tamas, Cuttat-Theurillat, Rachel, Waldt, Annick, Papasaikas, Panagiotis, Diggelmann, Roland, Patino-Alvarez, Claudia P., Galliker, Patricia, Spirig, Stefan, Pavlinic, Dinko, Gerber-Hollbach, Nadine, Schuierer, Sven, Srdanovic, Aldin, Balogh, Marton, Panero, Riccardo, Kusnyerik, Akos, Szabo, Arnold, Stadler, Michael, Orgül, Selim, Picelli, Simone, Hasler, Pascal W., Hierlemann, Andreas, Scholl, Hendrik P. N., Roma, Guglielmo, Nigsch, Florian, Roska, Botond

الوصف: How closely human organoids recapitulate cell-type diversity and cell-type maturation of their target organs is not well understood. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers. We sequenced the RNA of 158,844 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable ‘developed’ state at a rate similar to human retina development in vivo and the transcriptomes of organoid cell types converged towards the transcriptomes of adult peripheral retinal cell types. The expression of disease-associated genes was significantly cell-type specific in adult retina and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.

العلاقة: Cowan, Cameron, Renner, Magdalena, De Gennaro, Martina, Gross-Scherf, Brigitte, Goldblum, David, Hou, Yanyan, Munz, Martin, Rodrigues, Tiago M., Krol, Jacek, Szikra, Tamas, Cuttat-Theurillat, Rachel, Waldt, Annick, Papasaikas, Panagiotis, Diggelmann, Roland, Patino-Alvarez, Claudia P., Galliker, Patricia, Spirig, Stefan, Pavlinic, Dinko, Gerber-Hollbach, Nadine, Schuierer, Sven, Srdanovic, Aldin, Balogh, Marton, Panero, Riccardo, Kusnyerik, Akos, Szabo, Arnold, Stadler, Michael, Orgül, Selim, Picelli, Simone, Hasler, Pascal W., Hierlemann, Andreas, Scholl, Hendrik P. N., Roma, Guglielmo, Nigsch, Florian and Roska, Botond (2020) Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map. Cell, 182 (6). p. 1623. ISSN 00928674

الإتاحة: https://doi.org/10.1016/j.cell.2020.08.013Test
https://oak.novartis.com/42817Test/
https://www.cell.com/cell/fulltext/S0092-8674Test(20)31004-7