High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology

Sybil R.L. Stacpoole; Sonia Spitzer; Bilada Bilican; Alastair Compston; Ragnhildur Karadottir; Siddharthan Chandran; Robin J.M. Franklin

doi:10.1016/j.stemcr.2013.09.006

High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology

Sybil R.L. Stacpoole^*, Sonia Spitzer, Bilada Bilican, Alastair Compston, Ragnhildur Karadottir, Siddharthan Chandran, Robin J.M. Franklin

^*Corresponding author for this work

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

61 Citations (Scopus)

Abstract

We have established and efficient system to specify NG2/PDGF-Rα/ OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at low, physiological (3%) oxygen levels. This was achieved via both forebrain and spinal cord origins, with up to 98% of cells expressing NG2. Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction via ventral forebrain pathways. The OPCs mature in vitro to express O4 (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic protein-positive (MBP+) multibranching oligodendrocytes. These were cultured alongside hESC-derived neurons. The electrophysiological properties of human OPCs are similar to those of rat OPCs, with large voltage-gated sodium currents and the ability to fire action potentials. Exposure to a selective retinoid X receptor agonist increased the proportion of O4+ oligodendrocytes that express MBP from 5% to 30%. Thus, we have established a developmentally engineered system to investigate the biological properties of human OPCs and test the effects of putative remyelinating agents prior to clinical application.

Original language	English
Pages (from-to)	437-450
Number of pages	14
Journal	Stem Cell Reports
Volume	1
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2013.09.006
Publication status	Published - 19 Nov 2013

Bibliographical note

Funding Information:
This work was supported by the Multiple Sclerosis Society UK, the Evelyn Trust, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (Cambridge Biomedical Research Centre). S.R.L.S. was supported by a Sir David Walker Fellowship, a joint Medical Research Council and Multiple Sclerosis Society Clinical Research Training Fellowship (No. G0800487), and a Raymond and Beverly Sackler Studentship.

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title = "High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology",

abstract = "We have established and efficient system to specify NG2/PDGF-Rα/ OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at low, physiological (3%) oxygen levels. This was achieved via both forebrain and spinal cord origins, with up to 98% of cells expressing NG2. Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction via ventral forebrain pathways. The OPCs mature in vitro to express O4 (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic protein-positive (MBP+) multibranching oligodendrocytes. These were cultured alongside hESC-derived neurons. The electrophysiological properties of human OPCs are similar to those of rat OPCs, with large voltage-gated sodium currents and the ability to fire action potentials. Exposure to a selective retinoid X receptor agonist increased the proportion of O4+ oligodendrocytes that express MBP from 5% to 30%. Thus, we have established a developmentally engineered system to investigate the biological properties of human OPCs and test the effects of putative remyelinating agents prior to clinical application.",

author = "Stacpoole, {Sybil R.L.} and Sonia Spitzer and Bilada Bilican and Alastair Compston and Ragnhildur Karadottir and Siddharthan Chandran and Franklin, {Robin J.M.}",

note = "Funding Information: This work was supported by the Multiple Sclerosis Society UK, the Evelyn Trust, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (Cambridge Biomedical Research Centre). S.R.L.S. was supported by a Sir David Walker Fellowship, a joint Medical Research Council and Multiple Sclerosis Society Clinical Research Training Fellowship (No. G0800487), and a Raymond and Beverly Sackler Studentship. ",

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AU - Spitzer, Sonia

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AU - Compston, Alastair

AU - Karadottir, Ragnhildur

AU - Chandran, Siddharthan

AU - Franklin, Robin J.M.

N1 - Funding Information: This work was supported by the Multiple Sclerosis Society UK, the Evelyn Trust, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (Cambridge Biomedical Research Centre). S.R.L.S. was supported by a Sir David Walker Fellowship, a joint Medical Research Council and Multiple Sclerosis Society Clinical Research Training Fellowship (No. G0800487), and a Raymond and Beverly Sackler Studentship.

PY - 2013/11/19

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N2 - We have established and efficient system to specify NG2/PDGF-Rα/ OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at low, physiological (3%) oxygen levels. This was achieved via both forebrain and spinal cord origins, with up to 98% of cells expressing NG2. Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction via ventral forebrain pathways. The OPCs mature in vitro to express O4 (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic protein-positive (MBP+) multibranching oligodendrocytes. These were cultured alongside hESC-derived neurons. The electrophysiological properties of human OPCs are similar to those of rat OPCs, with large voltage-gated sodium currents and the ability to fire action potentials. Exposure to a selective retinoid X receptor agonist increased the proportion of O4+ oligodendrocytes that express MBP from 5% to 30%. Thus, we have established a developmentally engineered system to investigate the biological properties of human OPCs and test the effects of putative remyelinating agents prior to clinical application.

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High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology

Abstract

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