title: Fast and efficient neural conversion of human hematopoietic cells.
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.
authors.affiliation: Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Castaño
authors.affiliation: Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Menendez
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bruzos-Cidon
authors.affiliation: Department of Cell Biology, Immunology and Neurosciences, Faculty of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain; Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona 08036, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Straccia
authors.affiliation: Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Sousa
authors.affiliation: Cell Reprogramming and Differentiation Platform, Inbiomed, San Sebastian 20009, Spain.
authors.forename: Lorea
authors.initials: L
authors.lastname: Zabaleta
authors.affiliation: Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Vazquez
authors.affiliation: Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain; Cell Reprogramming and Differentiation Platform, Inbiomed, San Sebastian 20009, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Zubiarrain
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Kai-Christian
authors.initials: KC
authors.lastname: Sonntag
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ugedo
authors.affiliation: Cell Reprogramming and Differentiation Platform, Inbiomed, San Sebastian 20009, Spain.
authors.forename: Xonia
authors.initials: X
authors.lastname: Carvajal-Vergara
authors.affiliation: Department of Cell Biology, Immunology and Neurosciences, Faculty of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain; Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona 08036, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Canals
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Torrecilla
authors.affiliation: Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain. Electronic address: rpernaute@inbiomed.org.
authors.forename: Rosario
authors.initials: R
authors.lastname: Sanchez-Pernaute
authors.affiliation: Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain. Electronic address: agiorgetti@carrerasresearch.org.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgetti
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008564:Membrane Potentials; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010641:Phenotype
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides