Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity

Bibliographic Details
Title: Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity
Authors: Jong-Hee Lee, Ryan R. Mitchell, Jamie D. McNicol, Zoya Shapovalova, Sarah Laronde, Borko Tanasijevic, Chloe Milsom, Fanny Casado, Aline Fiebig-Comyn, Tony J. Collins, Karun K. Singh, Mickie Bhatia
Source: Cell Reports, Vol 11, Iss 9, Pp 1367-1376 (2015)
Publisher Information: Elsevier, 2015.
Publication Year: 2015
Collection: LCC:Biology (General)
Subject Terms: Biology (General), QH301-705.5
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2211-1247
Relation: http://www.sciencedirect.com/science/article/pii/S2211124715004738; https://doaj.org/toc/2211-1247
DOI: 10.1016/j.celrep.2015.04.056
Access URL: https://doaj.org/article/b11aa922158d4166b81be9280ad2f0aa
Accession Number: edsdoj.b11aa922158d4166b81be9280ad2f0aa
Database: Directory of Open Access Journals
More Details
ISSN:22111247
DOI:10.1016/j.celrep.2015.04.056
Published in:Cell Reports
Language:English