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Fast and Efficient Neural Conversion of Human Hematopoietic Cells

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Date
2014-12-09
Author
Castaño, Julio
Menéndez, Pablo
Bruzos Cidón, Cristina
Straccia, Marco
Sousa, Amaia
Zabaleta, Lorea
Vázquez, Nerea
Zubiarrain, Amaia
Sonntag, Kai-Christian
Ugedo Urruela, Luisa
Carvajal-Vergara, Xonia
Canals, Josep Maria
Torrecilla Sesma, María
Sánchez-Pernaute, Rosario
Giorgetti, Alessandra
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Stem Cell Reports 3 (6) : 1118-1131 (2014)
URI
http://hdl.handle.net/10810/15770
Abstract
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.
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