Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells

2010 ◽  
Vol 89 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Asuka Morizane ◽  
Daisuke Doi ◽  
Tetsuhiro Kikuchi ◽  
Kaneyasu Nishimura ◽  
Jun Takahashi
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Small Molecule Inhibitors ◽  
Neural Induction ◽  
Human Pluripotent Stem Cells ◽  
Bone Morphogenic Protein ◽  
Highly Efficient

scholarly journals Small-Molecule-Driven Hepatocyte Differentiation of Human Pluripotent Stem Cells

2015 ◽  
Vol 4 (5) ◽  
pp. 939-952 ◽  
Author(s):  
Richard Siller ◽  
Sebastian Greenhough ◽  
Elena Naumovska ◽  
Gareth J. Sullivan
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Hepatocyte Differentiation

scholarly journals Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Stephanie F Bellmaine ◽  
Dmitry A Ovchinnikov ◽  
David T Manallack ◽  
Claire E Cuddy ◽  
Andrew G Elefanty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Gene Dosage ◽  
Gene Activation ◽  
Neural Induction ◽  
Neural Progenitor Cell ◽  
Human Pluripotent Stem Cells ◽  
Mammalian Development ◽  
Neural Lineage ◽  
Early Mammalian Development

Genetic analysis has revealed that the dual specificity protein kinase DYRK1A has multiple roles in the development of the central nervous system. Increased DYRK1A gene dosage, such as occurs in Down syndrome, is known to affect neural progenitor cell differentiation, while haploinsufficiency of DYRK1A is associated with severe microcephaly. Using a set of known and newly synthesized DYRK1A inhibitors, along with CRISPR-mediated gene activation and shRNA knockdown of DYRK1A, we show here that chemical inhibition or genetic knockdown of DYRK1A interferes with neural specification of human pluripotent stem cells, a process equating to the earliest stage of human brain development. Specifically, DYRK1A inhibition insulates the self-renewing subpopulation of human pluripotent stem cells from powerful signals that drive neural induction. Our results suggest a novel mechanism for the disruptive effects of the absence or haploinsufficiency of DYRK1A on early mammalian development, and reveal a requirement for DYRK1A in the acquisition of competence for differentiation in human pluripotent stem cells.

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