NPTX1 regulates neural lineage specification from human pluripotent stem cells

Cell Rep. 2014 Feb 27;6(4):724-36. doi: 10.1016/j.celrep.2014.01.026. Epub 2014 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Bone Morphogenetic Proteins / metabolism
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Lineage*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis
  • Protein Binding
  • Transcriptome
  • Up-Regulation


  • Bone Morphogenetic Proteins
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • TDGF1 protein, human
  • neuronal pentraxin
  • C-Reactive Protein

Associated data

  • GEO/GSE34551