Skip to main content
placeholder image

Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system

Journal Article


Download full-text (Open Access)

Abstract


  • The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named "caudal neural progenitors" (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube.

Authors


  •   Denham, Mark (external author)
  •   Hasegawa, Kouichi (external author)
  •   Menheniott, Trevelyan (external author)
  •   Rollo, Benjamin (external author)
  •   Zhang, Dongcheng (external author)
  •   Hough, Shelley (external author)
  •   Alshawaf, Abdullah (external author)
  •   Febbraro, Fabia (external author)
  •   Ighaniyan, Samiramis (external author)
  •   Leung, Jessie (external author)
  •   Elliott, David A. (external author)
  •   Newgreen, Donald F. (external author)
  •   Pera, Martin F. (external author)
  •   Dottori, Mirella

Publication Date


  • 2015

Citation


  • Denham, M., Hasegawa, K., Menheniott, T., Rollo, B., Zhang, D., Hough, S., Alshawaf, A., Febbraro, F., Ighaniyan, S., Leung, J., Elliott, D. A., Newgreen, D. F., Pera, M. F. & Dottori, M. (2015). Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system. Stem Cells, 33 (6), 1759-1770.

Scopus Eid


  • 2-s2.0-84929773702

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2184&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1158

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1759

End Page


  • 1770

Volume


  • 33

Issue


  • 6

Place Of Publication


  • United States

Abstract


  • The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named "caudal neural progenitors" (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube.

Authors


  •   Denham, Mark (external author)
  •   Hasegawa, Kouichi (external author)
  •   Menheniott, Trevelyan (external author)
  •   Rollo, Benjamin (external author)
  •   Zhang, Dongcheng (external author)
  •   Hough, Shelley (external author)
  •   Alshawaf, Abdullah (external author)
  •   Febbraro, Fabia (external author)
  •   Ighaniyan, Samiramis (external author)
  •   Leung, Jessie (external author)
  •   Elliott, David A. (external author)
  •   Newgreen, Donald F. (external author)
  •   Pera, Martin F. (external author)
  •   Dottori, Mirella

Publication Date


  • 2015

Citation


  • Denham, M., Hasegawa, K., Menheniott, T., Rollo, B., Zhang, D., Hough, S., Alshawaf, A., Febbraro, F., Ighaniyan, S., Leung, J., Elliott, D. A., Newgreen, D. F., Pera, M. F. & Dottori, M. (2015). Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system. Stem Cells, 33 (6), 1759-1770.

Scopus Eid


  • 2-s2.0-84929773702

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2184&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1158

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1759

End Page


  • 1770

Volume


  • 33

Issue


  • 6

Place Of Publication


  • United States