Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells

Yong Hee Rhee, Lesly Puspita, Yanuar Alan Sulistio, Seung Won Kim, Vincencius Vidyawan, Rosalie Elvira, Mi Yoon Chang, Jae won Shim, Sang-Hun Lee

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In this study, we found that undifferentiated human pluripotent stem cells (hPSCs; up to 30% of total cells) present in the cultures of neural stem or precursor cells (NPCs) completely disappeared within several days when cultured under neural differentiation culture conditions. Intriguingly, the disappearance of undifferentiated cells was not due to cell death but was instead mediated by neural conversion of hPSCs. Based on these findings, we propose pre-conditioning of donor NPC cultures under terminal differentiation culture conditions as a simple but efficient method of eliminating undifferentiated cells to treat neurologic disorders. In addition, we could establish a new neural differentiation protocol, in which undifferentiated hPSCs co-cultured with NPCs become differentiated neurons or NPCs in an extremely efficient, fast, and reproducible manner across the hESC and human-induced pluripotent stem cell (hiPSC) lines. Rhee et al. report that residual expression of OCT3/4 in NPC cultures disappears within days when cultured under neural differentiation culture condition. The authors further propose that hPSCs co-cultured with hESC-derived NPCs become NPCs or neurons in an efficient and reproducible manner across multiple hPSC lines.

Original languageEnglish
Pages (from-to)1299-1312
Number of pages14
JournalMolecular Therapy
Volume27
Issue number7
DOIs
StatePublished - 2019 Jul 3

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Cell Culture Techniques
Neurons
Induced Pluripotent Stem Cells
Pluripotent Stem Cells
Neural Stem Cells
Nervous System Diseases
Cell Death
Cell Line
Human Embryonic Stem Cells

Keywords

  • co-culture
  • human pluripotent stem cells
  • neural differentiation
  • neural precursor cells

Cite this

Rhee, Yong Hee ; Puspita, Lesly ; Sulistio, Yanuar Alan ; Kim, Seung Won ; Vidyawan, Vincencius ; Elvira, Rosalie ; Chang, Mi Yoon ; Shim, Jae won ; Lee, Sang-Hun. / Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells. In: Molecular Therapy. 2019 ; Vol. 27, No. 7. pp. 1299-1312.
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Rhee, YH, Puspita, L, Sulistio, YA, Kim, SW, Vidyawan, V, Elvira, R, Chang, MY, Shim, JW & Lee, S-H 2019, 'Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells', Molecular Therapy, vol. 27, no. 7, pp. 1299-1312. https://doi.org/10.1016/j.ymthe.2019.04.011

Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells. / Rhee, Yong Hee; Puspita, Lesly; Sulistio, Yanuar Alan; Kim, Seung Won; Vidyawan, Vincencius; Elvira, Rosalie; Chang, Mi Yoon; Shim, Jae won; Lee, Sang-Hun.

In: Molecular Therapy, Vol. 27, No. 7, 03.07.2019, p. 1299-1312.

Research output: Contribution to journalArticleResearchpeer-review

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