Modeling physiological and pathological human neurogenesis in the dish

Area of Science:

• Stem cell biology
• Neuroscience
• Developmental biology

Background:

• Advances in directing neuronal differentiation of human pluripotent stem cells (hPSCs) enable modeling of early neurogenesis.
• hPSC-derived neural rosettes mimic the developing neural tube's architecture and function.
• Epigenetic stimulation can guide rosette neural progenitors toward specific neuronal subtypes and neural crest derivatives.

Purpose of the Study:

• To review the progress and challenges in using hPSCs for modeling neurogenesis and neural development.
• To highlight the potential of hPSC-derived neural tissues in understanding human brain development and diseases.
• To discuss advancements in neuronal maturation and in vitro cell aging for therapeutic applications.

Main Methods:

• Utilizing human embryonic and induced pluripotent stem cells (hPSCs) for neuronal differentiation.
• Employing epigenetic stimulation methods to modulate neural progenitor identity.
• Developing innovative in vitro systems for three-dimensional self-organization of neural tissues.
• Establishing procedures for promoting maturation and accelerating aging of hPSC-derived neurons.

Main Results:

• hPSC-derived neural rosettes serve as in vitro models for early neurogenesis and neural tube development.
• Self-organizing three-dimensional neural tissues derived from hPSCs demonstrate complex developmental capacity.
• New procedures enhance the maturation and functionality of hPSC-derived neurons.
• Methods for accelerating in vitro cell aging are under development.

Conclusions:

• hPSC technology provides a robust model system for studying early and late neurogenesis.
• This system is crucial for understanding human brain development and investigating disease mechanisms.
• Further development is needed to overcome hurdles in modeling late-onset disorders and for cell replacement therapies.