title: Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity.
abstract: The clinical applicability of direct cell fate conversion depends on obtaining tissue from patients that is easy to harvest, store, and manipulate for reprogramming. Here, we generate induced neural progenitor cells (iNPCs) from neonatal and adult peripheral blood using single-factor OCT4 reprogramming. Unlike fibroblasts that share molecular hallmarks of neural crest, OCT4 reprogramming of blood was facilitated by SMAD+GSK-3 inhibition to overcome restrictions on neural fate conversion. Blood-derived (BD) iNPCs differentiate in vivo and respond to guided differentiation in vitro, producing glia (astrocytes and oligodendrocytes) and multiple neuronal subtypes, including dopaminergic (CNS related) and nociceptive neurons (peripheral nervous system [PNS]). Furthermore, nociceptive neurons phenocopy chemotherapy-induced neurotoxicity in a system suitable for high-throughput drug screening. Our findings provide an easily accessible approach for generating human NPCs that harbor extensive developmental potential, enabling the study of clinically relevant neural diseases directly from patient cohorts.
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Mitchell
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Jamie D
authors.initials: JD
authors.lastname: McNicol
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Shapovalova
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Laronde
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Borko
authors.initials: B
authors.lastname: Tanasijevic
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Chloe
authors.initials: C
authors.lastname: Milsom
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Fanny
authors.initials: F
authors.lastname: Casado
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Aline
authors.initials: A
authors.lastname: Fiebig-Comyn
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Collins
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Karun K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada. Electronic address: mbhatia@mcmaster.ca.
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human