Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders

Nora Urraca, Rawaha Memon, Ikbale El-Iyachi, Sarita Goorha, Colleen Valdez, Quynh T. Tran, Reese Scroggs, Gustavo Miranda-Carboni, Martin Donaldson, Dave Bridges, Lawrence Reiter

Research output: Contribution to journalArticle

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Abstract

A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs) are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSCs. We immortalized control DPSCs using human telomerase reverse transcriptase (hTERT) and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSCs share morphological and electrophysiological properties with non-immortalized DPSCs. We also show that differentiation of DPSCs into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NRSF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSCs can be obtained from teeth stored for ≥. 72. h, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSCs for the study of disease.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalStem Cell Research
Volume15
Issue number3
DOIs
StatePublished - Nov 1 2015

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Dental Pulp
Stem Cells
Neurons
Gene Expression
Tooth
Multipotent Stem Cells
Translational Medical Research
Deciduous Tooth
RNA

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders. / Urraca, Nora; Memon, Rawaha; El-Iyachi, Ikbale; Goorha, Sarita; Valdez, Colleen; Tran, Quynh T.; Scroggs, Reese; Miranda-Carboni, Gustavo; Donaldson, Martin; Bridges, Dave; Reiter, Lawrence.

In: Stem Cell Research, Vol. 15, No. 3, 01.11.2015, p. 722-730.

Research output: Contribution to journalArticle

Urraca, Nora ; Memon, Rawaha ; El-Iyachi, Ikbale ; Goorha, Sarita ; Valdez, Colleen ; Tran, Quynh T. ; Scroggs, Reese ; Miranda-Carboni, Gustavo ; Donaldson, Martin ; Bridges, Dave ; Reiter, Lawrence. / Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders. In: Stem Cell Research. 2015 ; Vol. 15, No. 3. pp. 722-730.
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