The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF.
Neural rosettes derived from human induced pluripotent stem cells (iPSCs) have been claimed to be a highly robust in vitro cellular model for biomedical application. They are able to propagate in vitro in the presence of mitogens, including basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). However, these two mitogens are also involved in anterior-posterior patterning in a gradient dependent manner along the neural tube axis. Here, we compared the regional identity of neural rosette cells and specific neural subtypes of their progeny propagated with low and high concentrations of bFGF and EGF. We observed that low concentrations of bFGF and EGF in the culturing system were able to induce forebrain identity of the neural rosettes and promote subsequent cortical neuronal differentiation. On the contrary, high concentrations of these mitogens stimulate a mid-hindbrain fate of the neural rosettes, resulting in subsequent cholinergic neuron differentiation. Thus, our results indicate that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells.
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: zhou@sund.ku.dk.
Shuling
S
Zhou
BioTalentum Ltd., Gödöllő, Hungary; Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllő, Hungary. Electronic address: Anna.Ochalek@biotalentum.hu.
Anna
A
Ochalek
BioTalentum Ltd., Gödöllő, Hungary. Electronic address: Karolina.Szczesna@biotalentum.hu.
Karolina
K
Szczesna
BioTalentum Ltd., Gödöllő, Hungary; Department of Medical Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary. Electronic address: Hasan.Avci@biotalentum.hu.
Hasan X
HX
Avci
BioTalentum Ltd., Gödöllő, Hungary. Electronic address: Julianna.Kobolak@biotalentum.hu.
Julianna
J
Kobolák
BioTalentum Ltd., Gödöllő, Hungary; Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllő, Hungary. Electronic address: soszter@gmail.com.
Eszter
E
Varga
Bioneer A/S, Hoersholm, Denmark. Electronic address: mar@bioneer.dk.
Mikkel
M
Rasmussen
Bioneer A/S, Hoersholm, Denmark. Electronic address: bho@bioneer.dk.
Bjørn
B
Holst
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: scs@sund.ku.dk.
Susanna
S
Cirera
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: poh@sund.ku.dk.
Poul
P
Hyttel
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: kkf@sund.ku.dk.
Kristine K
KK
Freude
BioTalentum Ltd., Gödöllő, Hungary; Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllő, Hungary; Departments of Equine Sciences and Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands. Electronic address: andras.dinnyes@biotalentum.hu.
András
A
Dinnyés
D002454:Cell Differentiation / Q000235:genetics*; D059329:Cholinergic Neurons / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008934:Mitogens / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D054259:Neural Tube / Q000254:growth & development / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*
D008934:Mitogens; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor
Cholinergic neurons; Forebrain NPCs; Glutamatergic neurons; Mid-hindbrain NPCs; Mitogens; Neural rosette