Fast and Efficient Neural Conversion of Human Hematopoietic Cells

Julio Castaño, Pablo Menendez, Cristina Bruzos-Cidon, Marco Straccia, Amaia Sousa, Lorea Zabaleta, Nerea Vazquez, Amaia Zubiarrain, Kai-Christian Sonntag, Luisa Ugedo, Xonia Carvajal-Vergara, Josep Maria Canals, Maria Torrecilla, Rosario Sanchez-Pernaute, Alessandra Giorgetti

Neurons obtained directly from human somatic cells hold great promise for disease modeling and drug screening. Available protocols rely on overexpression of transcription factors using integrative vectors and are often slow, complex, and inefficient. We report a fast and efficient approach for generating induced neural cells (iNCs) directly from human hematopoietic cells using Sendai virus. Upon SOX2 and c-MYC expression, CD133-positive cord blood cells rapidly adopt a neuroepithelial morphology and exhibit high expansion capacity. Under defined neurogenic culture conditions, they express mature neuronal markers and fire spontaneous action potentials that can be modulated with neurotransmitters. SOX2 and c-MYC are also sufficient to convert peripheral blood mononuclear cells into iNCs. However, the conversion process is less efficient and resulting iNCs have limited expansion capacity and electrophysiological activity upon differentiation. Our study demonstrates rapid and efficient generation of iNCs from hematopoietic cells while underscoring the impact of target cells on conversion efficiency.