Regional Manager, EMEA Bit Bio Ltd Cambridge, England, United Kingdom
Abstract: Oligodendrocytes (OLs) are the myelinating cells in the central nervous system. By ensheathing axons, OLs enhance the action potential conduction velocity. OLs arise from oligodendrocyte precursor cells (OPCs) during pre- and postnatal development. The death of OLs and the impairment of differentiation of OPCs into OLs is a major pathological characteristic in demyelinating diseases.
The development of therapies that promote myelination in neurological conditions, particularly demyelinating diseases, is hampered by the limited translatability of existing preclinical animal models, and the lack of reliable in vitro models. Human induced pluripotent stem cells (hiPSCs) can be used to generate OLs for in vitro applications, however, current differentiation protocols are often lengthy, challenging to reproduce, and are difficult to scale.
Our proprietary opti-ox™ (optimised inducible overexpression) technology enables highly controlled expression of transcription factors, deterministically programming hiPSCs into specific cell types of interest, to provide a robust, consistent, and reliable source of human cells for in vitro applications.
We have used opti-ox to rapidly program hiPSCs into oligodendrocyte-like cells (ioOligodendrocyte-like cells), a population of oligodendroglial cells resembling a pre-myelinating oligodendrocyte state. By day 1, the cells present an OPC-like morphology and are positive for oligodendroglial lineage markers OLIG2, SOX10 and O4. By day 8, the cells show increased complexity with an OL-like morphology, and increased expression of other mature oligodendrocyte markers such as MBP, MAL, CNP and MYRF, seen by qRT-PCR, bulk RNA and scRNAseq. Furthermore, whole transcriptome analysis demonstrates equivalent expression profiles between three different manufactured lots indicating consistency and experimental reproducibility.
ioOligodendrocyte-like cells provide a relevant, consistent, and scalable source of human cells that can be used for investigations into novel therapeutics and molecular mechanisms that regulate this critical glial cell type that is implicated in various human diseases.
