title: A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.
abstract: Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self-renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing. Here we used an unbiased transcriptomic analysis to characterize in vitro culture of human NPCs and to define the gene expression programs activated during the differentiation of these cells into astrocytes using FBS or the combination of CNTF and BMP4. Our results demonstrate that in vitro cultures of human NPCs isolated during the gliogenic phase of neurodevelopment mainly consist of radial glial cells (RGCs) and glia-restricted progenitor cells. In these cells the combination of CNTF and BMP4 activates the JAK/STAT and SMAD signaling cascades, leading to the inhibition of oligodendrocytes lineage commitment and activation of astrocytes differentiation. On the other hand, FBS-derived astrocytes have properties of reactive astrocytes. Our work suggests that in vitro culture of human NPCs represents a valuable cellular system to study human disorders characterized by impairment of astrocytes development and function. Our datasets represent an important resource for researchers studying human astrocytes development and might set the basis for the discovery of novel human-specific astrocyte markers.
authors: Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, 1501 NW 10th Ave, BRB 508, Miami, FL, 33136, USA.
authors: Marco
authors: M
authors: Magistri
authors: Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, 1501 NW 10th Ave, BRB 508, Miami, FL, 33136, USA.
authors: Nathalie
authors: N
authors: Khoury
authors: Department of Life Sciences, Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
authors: Emilia Maria Cristina
authors: EM
authors: Mazza
authors: Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, 1501 NW 10th Ave, BRB 508, Miami, FL, 33136, USA.
authors: Dmitry
authors: D
authors: Velmeshev
authors: Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Jae K
authors: JK
authors: Lee
authors: Department of Life Sciences, Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
authors: Silvio
authors: S
authors: Bicciato
authors: Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Pantelis
authors: P
authors: Tsoulfas
authors: Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, 1501 NW 10th Ave, BRB 508, Miami, FL, 33136, USA.
authors: Mohammad Ali
authors: MA
authors: Faghihi
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D020934:Ciliary Neurotrophic Factor; D050791:STAT Transcription Factors; D051785:Smad Proteins; D053612:Janus Kinases
keywords: gliogenesis; human astrocytes; neural progenitor cells; neurodevelopment; radial glial cells; transcriptomic