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3D ECM-rich environment sustains the identity of naive human iPSCs.
Cesare, Elisa; Urciuolo, Anna; Stuart, Hannah T; Torchio, Erika; Gesualdo, Alessia; Laterza, Cecilia; Gagliano, Onelia; Martewicz, Sebastian; Cui, Meihua; Manfredi, Anna; Di Filippo, Lucio; Sabatelli, Patrizia; Squarzoni, Stefano; Zorzan, Irene; Betto, Riccardo M; Martello, Graziano; Cacchiarelli, Davide; Luni, Camilla; Elvassore, Nicola.
Afiliación
  • Cesare E; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy.
  • Urciuolo A; University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; Institute of Pediatric Research IRP, Corso Stati Uniti, Padova 35127, Italy; Department of Molecular Medicine, University of Padova, Via G. Colombo 3, 35131 Padova, Italy.
  • Stuart HT; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Research Institute of Molecular Pathology (IMP), Vienna BioCen
  • Torchio E; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy.
  • Gesualdo A; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy.
  • Laterza C; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy.
  • Gagliano O; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy.
  • Martewicz S; Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China.
  • Cui M; Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China.
  • Manfredi A; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy; Next Generation Diagnostic srl, Pozzuoli, Italy.
  • Di Filippo L; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy; Next Generation Diagnostic srl, Pozzuoli, Italy.
  • Sabatelli P; CNR - Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" - Unit of Bologna, Bologna, Italy; IRCCS-Istituto Ortopedico Rizzoli, Bologna, Italy.
  • Squarzoni S; CNR - Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" - Unit of Bologna, Bologna, Italy; IRCCS-Istituto Ortopedico Rizzoli, Bologna, Italy.
  • Zorzan I; Epigenetics Programme, Babraham Institute, CB22 3AT Cambridge, UK.
  • Betto RM; Department of Molecular Medicine, University of Padova, Via G. Colombo 3, 35131 Padova, Italy.
  • Martello G; Department of Biology, University of Padova, Via G. Colombo 3, Padova 35131, Italy.
  • Cacchiarelli D; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy; Department of Translational Medicine, University of Naples "Federico II", Naples, Italy; School for Advanced Studies, Genomics and Experimental Medicine Program, University of N
  • Luni C; Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China; Department of Civil, Chemical, Environmental, and Materials Engineering (DICAM), University of Bologna, Via Terracini 28, Bologna 40131, Italy.
  • Elvassore N; Department of Industrial Engineering, University of Padova, 6/a Via Gradenigo, Padova 35131, Italy; Veneto Institute of Molecular Medicine, 2 Via Orus, Padova 35131, Italy; University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. Electronic ad
Cell Stem Cell ; 29(12): 1703-1717.e7, 2022 12 01.
Article en En | MEDLINE | ID: mdl-36459970
ABSTRACT
The establishment of in vitro naive human pluripotent stem cell cultures opened new perspectives for the study of early events in human development. The role of several transcription factors and signaling pathways have been characterized during maintenance of human naive pluripotency. However, little is known about the role exerted by the extracellular matrix (ECM) and its three-dimensional (3D) organization. Here, using an unbiased and integrated approach combining microfluidic cultures with transcriptional, proteomic, and secretome analyses, we found that naive, but not primed, hiPSC colonies are characterized by a self-organized ECM-rich microenvironment. Based on this, we developed a 3D culture system that supports robust long-term feeder-free self-renewal of naive hiPSCs and also allows direct and timely developmental morphogenesis simply by modulating the signaling environment. Our study opens new perspectives for future applications of naive hiPSCs to study critical stages of human development in 3D starting from a single cell.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Madre Pluripotentes / Células Madre Pluripotentes Inducidas Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2022 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Madre Pluripotentes / Células Madre Pluripotentes Inducidas Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2022 Tipo del documento: Article País de afiliación: Italia