Image_1_TGF-β1 Suppresses Proliferation and Induces Differentiation in Human iPSC Neural in vitro Models.TIF (4.6 MB)

Image_1_TGF-β1 Suppresses Proliferation and Induces Differentiation in Human iPSC Neural in vitro Models.TIF

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posted on 28.10.2020, 04:29 by Julia Izsak, Dzeneta Vizlin-Hodzic, Margarita Iljin, Joakim Strandberg, Janusz Jadasz, Thomas Olsson Bontell, Stephan Theiss, Eric Hanse, Hans Ågren, Keiko Funa, Sebastian Illes

Persistent neural stem cell (NSC) proliferation is, among others, a hallmark of immaturity in human induced pluripotent stem cell (hiPSC)-based neural models. TGF-β1 is known to regulate NSCs in vivo during embryonic development in rodents. Here we examined the role of TGF-β1 as a potential candidate to promote in vitro differentiation of hiPSCs-derived NSCs and maturation of neuronal progenies. We present that TGF-β1 is specifically present in early phases of human fetal brain development. We applied confocal imaging and electrophysiological assessment in hiPSC-NSC and 3D neural in vitro models and demonstrate that TGF-β1 is a signaling protein, which specifically suppresses proliferation, enhances neuronal and glial differentiation, without effecting neuronal maturation. Moreover, we demonstrate that TGF-β1 is equally efficient in enhancing neuronal differentiation of human NSCs as an artificial synthetic small molecule. The presented approach provides a proof-of-concept to replace artificial small molecules with more physiological signaling factors, which paves the way to improve the physiological relevance of human neural developmental in vitro models.

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