Stem Cells

This course provides a comprehensive exploration of stem cells, examining their roles in development, regeneration, and disease modeling, with a particular emphasis on neural cells and human brain organoids. The curriculum commences with an overview of fundamental stem cell properties, including their diverse niches across various tissues.

Subsequently, the course transitions to the critical function of radial glial progenitors in neurogenesis and the intricate dynamics of the adult neural stem cell (NSC) niche, analyzing key signaling pathways that regulate their maintenance and activity. A review of other pertinent adult stem cell types, such as intestinal and mesenchymal stem cells, will also be conducted.

A substantial segment of the course is dedicated to human model systems. This includes an examination of the molecular characteristics of pluripotent stem cells and the pivotal involvement of transcription factors, such as Sox2, in governing pluripotency and neural specification. The course will then explore the in vitro patterning of neuronal identities and the molecular principles underlying neocortical neuron specification and diversity, incorporating evolutionary considerations.

The course concludes with an in-depth analysis of human cerebral organoids. Students will gain an understanding of the methodologies for generating and utilizing these advanced 3D models to investigate normal human brain evolution, simulate neurodevelopmental diseases, and study complex conditions such as sporadic Alzheimer's disease. Furthermore, advanced techniques for modeling complete human cortical neural networks in vitro and assessing excitatory/inhibitory (E/I) balance will be covered. This course aims to provide a robust understanding of the cellular and molecular mechanisms underpinning stem cell biology and their applications in neuroscience research.

Lesson Structure:

• Lessons 1-5: Introduction to stem cell fundamentals, including niches (hematopoietic, germline), radial glial progenitors, and the adult neural stem cell (NSC) niche, with an emphasis on SHH signaling.
• Lesson 6: Overview of additional adult stem cell types.
• Lessons 7-9: Discussion of human model systems, pluripotent stem cells, and the role of Sox2.
• Lessons 10-12: Exploration of in vitro patterning of neuronal identities, neocortical neuron specification, and diversity.
• Lessons 13-20: Detailed examination of human cerebral organoids, their application in modeling brain evolution, neurodevelopmental diseases, and sporadic Alzheimer's disease, alongside advanced techniques for studying neural networks and E/I balance.