title: Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells.
abstract: The balance of bone morphogenic protein (BMP), transforming growth factor-β (TGFβ)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small-molecule inhibitors of BMP (Dorsomorphin) and TGFβ/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder-free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine.
authors.affiliation: Department of Biological Repair, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Morizane
authors.forename: Daisuke
authors.initials: D
authors.lastname: Doi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Kaneyasu
authors.initials: K
authors.lastname: Nishimura
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors*; D001549:Benzamides / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D004149:Dioxoles / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055457:Nodal Protein / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D019485:Bone Morphogenetic Proteins; D004149:Dioxoles; D055457:Nodal Protein; D011720:Pyrazoles; D011743:Pyrimidines; D028341:Activins; C516138:dorsomorphin