Generation of Anterior Hindbrain-Specific, Glial-Restricted Progenitor-Like Cells from Human Pluripotent Stem Cells

Yun, Wonjin; Hong, Wonjun; Son, Daryeon; Liu, Hui Wen; Kim, Seung Soo; Park, Minji; Kim, In Yong; Kim, Dae Sung; Song, Gwonhwa; You, Seungkwon

doi:10.1089/scd.2019.0033

Cited by 10 publications

(13 citation statements)

References 56 publications

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“…These results were consistent with previous study showing that miconazole‐treatment resulted in robust generation of MBP + cells 23 . Furthermore, MACS‐purified O4 + oligodendrocytes in miconazole‐treated spheroids were engrafted into MBP‐deficient shiverer mice by the method, as previously reported 16 and these transplanted cells resulted in MBP + oligodendrocytes (Figure 3J) as well as contributed to myelin compaction after 12 weeks of transplantation, detected by electron microscopy (Figure 3K).…”

Section: Resultssupporting

confidence: 92%

“…This article describes a three-dimensional (3D) culture system, specifically 3D cerebral organoids (spheroids) that rapidly gen- separate cerebral regions. 20 Furthermore, this 3D culture approach contributed to rapid and efficient production of GFAP + astrocytes compared to our previous monolayer culture 16 (Figure 2F). These findings suggest that pre-OPCs-derived spheroids allow development of morphologically and immunologically diverse astrocytes in a rapid and efficient manner.…”

Section: Significance Statementmentioning

confidence: 83%

“…Spheroid culture starting from intermediate stage or precommitted stem/progenitor cells may facilitate the production of astrocytes and oligodendrocytes (Figure 4). Moreover, these OLIG2 and NKX2.2‐expressing pre‐OPCs could be propagated for 20 passages, 16 with repeated freeze‐thaw cycles, and continued to robustly express OLIG2 and NKX2.2, allowing reproducibility and repeatability by reduced batch‐to‐batch variability. Understanding the heterogeneity of inherent glial cells in terms of morphological, functional, and anatomical variations depending on different brain regions remains largely unknown 7,24,25 .…”

Section: Discussionmentioning

confidence: 99%

“…pNSCs and pre-OPCs were established and cultured as previously described. 16 The resulting neurospheres (>200 μm) were embedded in Matrigel droplets at day 4 as previously described. 11 Embedded neurospheres were cultured in appropriate conditions until 8 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we established primitive neural stem cells (pNSCs, expressing PAX6 and SOX1) and intermediate progenitor cells (expressing OLIG2 and NKX2.2) from hPSCs 16 . OLIG2 and NKX2.2‐expressing progenitor cells are known as preoligodendrocyte progenitor cells (pre‐OPCs) which are committed to SOX10 and PDGFRa‐expressing OPCs 17 .…”

Section: Introductionmentioning

confidence: 99%

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Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids

Yun

Kim

Song

et al. 2020

Stem Cells Translational Medicine

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Glial cells are crucial for the development of the central nervous system and the maintenance of chemical homeostasis. The process of gliogenesis has been well studied in the rodent brain, but it remains less well studied in the human brain. In addition, rodent glial cells differ from human counterparts in terms of morphologies, functions, and anatomical locations. Cerebral organoids (also referred to as spheroids) derived from human pluripotent stem cells (hPSCs) have been developed and are suitable cell‐based models for researching developmental and neurodegenerative diseases. The in vitro generation of glia, including astrocytes and oligodendrocytes, from such organoids represents a promising tool to model neuronal diseases. Here, we showed that three‐dimensional (3D) culture of OLIG2‐ and NKX2.2‐expressing neurospheres produced efficiently mature astrocytes and oligodendrocytes in terms of morphologies and expression pattern recapitulating native 3D environment. Our findings provide important insights for developmental research of the human brain and glial specification that may facilitate patient‐specific disease modeling.

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Section: Resultssupporting

confidence: 92%

Section: Significance Statementmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids

Yun

Kim

Song

et al. 2020

Stem Cells Translational Medicine

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Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes

Leventoux,

Morimoto,

Ishikawa

et al. 2024

Acta Neuropathol

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OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease

et al. 2022

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The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+ (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+ iOPCs was similar to that of O4+ OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development.

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Generation of Anterior Hindbrain-Specific, Glial-Restricted Progenitor-Like Cells from Human Pluripotent Stem Cells

Cited by 10 publications

References 56 publications

Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids

Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids

Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes

OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease

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