Retinoic Acid-Mediated Induction of Neurons and Glial Cells from Human Umbilical Cord-Derived Hematopoietic Stem Cells

Y. K. Jang, Joong Jean Park, M. C. Lee, B. H. Yoon, Y. S. Yang, S. E. Yang, Seung U. Kim

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Recent studies reporting trans-differentiation of mononucleated cells derived from human umbilical cord blood into neuronal cells aroused interest among investigators for their clinical implication and significance in regenerative medicine. In the present study, purified populations of hematopoietic stem cells were isolated via magnetic bead sorting and fluorescence-activated cell sorter (FACS) using a specific CD133 antibody, a cell type-specific marker for hematopoietic stem cells, and grown in culture in the presence of retinoic acid (RA). CD133+ hematopoietic stem cells expressed neuronal and glial phenotypes after RA treatment. RT-PCR analysis indicated that the RA treated CD133+ cells expressed mRNA transcripts for ATP-binding cassettes transporter ABCG2 (a universal stem cell marker), nestin (a specific cell type marker for neural stem cells), Musashi1 (a specific marker for neural stem cells) and RA receptors (RAR) including RAR-α, RAR-β, and retinoid X receptor (RXR)-γ. RA-treated CD133+ cells expressed mRNA transcripts for neuron-specific markers neurofilament proteins (NF-L, -M, -H) and synaptophysin as determined by RT-PCR, structural proteins characteristic of neurons including tubulin β III and neuron specific enolase (NSE) by Western blot, and neuron-specific markers NeuN and microtubule-associated protein-2 (MAP2) by immunocytochemistry. RA-treated CD133+ cells also expressed the astrocyte-specific marker glial fibrillary acidic protein (GFAP), as demonstrated by RT-PCR, Western blot, and immunocytochemistry. In addition, RA-treated CD133+ cells expressed cell type-specific markers for oligodendrocytes including myelin basic protein (MBP) as shown by RT-PCR, proteolipid protein (PLP) by Western blot analysis, and cyclic nucleotide phosphodiesterase (CNPase) by immunostaining. Upregulated expression of several basic helix-loop-helix (bHLH) transcription factors important for early neurogenesis, including Otx2, Pax6, Wnt1, Olig2, Hash1 and NeuroD1, was also demonstrated in CD133+ cells after RA treatment. These results indicate that human cord blood-derived CD133+ hematopoietic stem cells could trans-differentiate into neural cell types of neuron-like cells, astrocytes, and oligodendrocytes by RA treatment.

Original languageEnglish
Pages (from-to)573-584
Number of pages12
JournalJournal of Neuroscience Research
Volume75
Issue number4
DOIs
Publication statusPublished - 2004 Feb 15
Externally publishedYes

Fingerprint

Umbilical Cord
Hematopoietic Stem Cells
Tretinoin
Neuroglia
Neurons
Polymerase Chain Reaction
Neural Stem Cells
Western Blotting
Oligodendroglia
Fetal Blood
Astrocytes
Immunohistochemistry
Basic Helix-Loop-Helix Transcription Factors
Proteolipids
Retinoid X Receptors
Nestin
Messenger RNA
Synaptophysin
Retinoic Acid Receptors
Regenerative Medicine

Keywords

  • Human umbilical cord-derived hematopoietic stem cells
  • Neuronal differentiation
  • Retinoic acid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Retinoic Acid-Mediated Induction of Neurons and Glial Cells from Human Umbilical Cord-Derived Hematopoietic Stem Cells. / Jang, Y. K.; Park, Joong Jean; Lee, M. C.; Yoon, B. H.; Yang, Y. S.; Yang, S. E.; Kim, Seung U.

In: Journal of Neuroscience Research, Vol. 75, No. 4, 15.02.2004, p. 573-584.

Research output: Contribution to journalArticle

Jang, Y. K. ; Park, Joong Jean ; Lee, M. C. ; Yoon, B. H. ; Yang, Y. S. ; Yang, S. E. ; Kim, Seung U. / Retinoic Acid-Mediated Induction of Neurons and Glial Cells from Human Umbilical Cord-Derived Hematopoietic Stem Cells. In: Journal of Neuroscience Research. 2004 ; Vol. 75, No. 4. pp. 573-584.
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