SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

Abstract

SummaryScarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation.

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

“…The disadvantages are the time (it takes 55 to more than 200 days to generate O4+ late-stage oligodendrocyte progenitor cells) and costs of generating oligodendrocyte progenitor cells/oligodendrocytes. Recent developments have tried to accelerate extracellular lineage pattering by adding ectopic expression of cell-type determining transcription factors [105,106]. This approach allows hiPSCs to be differentiated to MBP+ oligodendrocytes within 22 days [106].…”

“…Recent developments have tried to accelerate extracellular lineage pattering by adding ectopic expression of cell-type determining transcription factors [105,106]. This approach allows hiPSCs to be differentiated to MBP+ oligodendrocytes within 22 days [106]. An additional advantage is the reduced cellular heterogeneity.…”

Stem cell derived oligodendrocytes to study myelin diseases

“…The majority of the differentiation protocols are based on in vitro patterning methods that recapitulate the fundamental steps of embryonic development by exploiting similar signaling cascades as described earlier (Alsanie, Niclis, & Petratos, ; Czepiel, Boddeke, & Copray, ; Hu, Du, & Zhang, ; Prasad et al, ). Here, we summarize briefly the basic principles to generate oligodendrocytes from human ESC and iPSC and include recent studies demonstrating that ectopic expression of transcription factors with key roles in OL development significantly accelerate the differentiation process (Ehrlich et al, ; Garcia‐Leon et al, ) (Figure ).…”

Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems

“…Although the major focus of Pawlowski et al and Rodrigues et al was to generate and characterize the iOPC stage, 137 , 138 Li et al, Ehrlich et al and García-León et al tried to reach the iOL stage as part of the main protocol. 135 , 136 , 139 Indeed, it is unclear whether protocol differences may have affected the properties of iOPCs or iOLs, e.g. with respect to kinetics and the efficiency of differentiation and myelination.…”