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

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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Engraftment of oligodendrocyte progenitor cells (OPCs), which form myelinating oligodendrocytes, has the potential to treat demyelinating diseases such as multiple sclerosis. However, conventional strategies for generating oligodendrocytes have mainly focused on direct differentiation into forebrain- or spinal cord-restricted oligodendrocytes without establishing or amplifying stem/progenitor cells. Taking advantage of a recently established culture system, we generated expandable EN1- and GBX2-positive glial-restricted progenitor-like cells (GPLCs) near the anterior hindbrain. These cells expressed PDGFRα, CD9, S100β, and SOX10 and mostly differentiated into GFAP-positive astrocytes and MBP-positive oligodendrocytes. RNA-seq analysis revealed that the transcriptome of GPLCs was similar to that of O4-positive OPCs, but distinct from that of rosette-type neural stem cells. Notably, engrafted GPLCs not only differentiated into GFAP-positive astrocytes but also myelinated the brains of adult shiverer mice 8 weeks after transplantation. Our strategy for establishing anterior hindbrain-specific GPLCs with gliogenic potency will facilitate their use in the treatment of demyelinating diseases and studies of the molecular mechanisms underlying glial development in the hindbrain.

Original languageEnglish
Pages (from-to)633-648
Number of pages16
JournalStem cells and development
Volume28
Issue number10
DOIs
Publication statusPublished - 2019 May 15

Bibliographical note

Funding Information:
This work was supported by Korea University Grant, the Bio & Medical Technology Development Program of the National Research Foundation of Korea, funded by the Korea Ministry of Science, ICT, & Future Planning (MSIP) project no. NRF-2015M3A9B4071074 and NRF-2015M3A9B4071076, a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2166), and the School of Life Sciences and Biotechnology for BK21 PLUS, Korea University.

Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.

Keywords

  • astrocytes
  • differentiation
  • glial restricted progenitor cells
  • hindbrain
  • oligodendrocytes

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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