title: NPTX1 regulates neural lineage specification from human pluripotent stem cells.
abstract: Neural induction is the first fundamental step in nervous system formation. During development, a tightly regulated niche modulates transient extracellular signals to influence neural lineage commitment. To date, however, the cascade of molecular events that sustain these signals in humans is not well understood. Here we show that NPTX1, a secreted protein, is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs). By manipulating its expression, we were able to reduce or initiate neural lineage commitment. A time-course transcriptome analysis and functional assays show that NPTX1 acts in part by binding the Nodal receptor cofactor TDGF1, reducing both Nodal and BMP signaling. Our findings identify one of the earliest genes expressed upon neural induction and provide insight into human neural lineage specification.
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA.
authors: Nathan C
authors: NC
authors: Boles
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA; Department of Biomedical Sciences, University at Albany, New York State University of New York, Albany, NY 12201, USA.
authors: Sarah E
authors: SE
authors: Hirsch
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA.
authors: Sheila
authors: S
authors: Le
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA; Department of Biomedical Sciences, University at Albany, New York State University of New York, Albany, NY 12201, USA.
authors: Barbara
authors: B
authors: Corneo
authors: Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Fadi
authors: F
authors: Najm
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA.
authors: Andrew P
authors: AP
authors: Minotti
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA.
authors: Qingjie
authors: Q
authors: Wang
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA.
authors: Steven
authors: S
authors: Lotz
authors: Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Paul J
authors: PJ
authors: Tesar
authors: The Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, USA; Department of Biomedical Sciences, University at Albany, New York State University of New York, Albany, NY 12201, USA. Electronic address: chrisfasano@neuralsci.org.
authors: Christopher A
authors: CA
authors: Fasano
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D011485:Protein Binding; D059467:Transcriptome; D015854:Up-Regulation; D000099153:Pentraxins
chemical_list: D019485:Bone Morphogenetic Proteins; D002097:C-Reactive Protein; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000099153:Pentraxins; C070636:TDGF1 protein, human