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Neurons made from teeth may be best for autism research

Posted by James Andrews on Wed, Nov 13, 2013 @ 03:03 PM

Tooth extraction: Neurons generated from baby teeth express high levels of a number of genes implicated in neurological disorders.In a study published in PLoS One, cells extracted from baby teeth, which fall out on their own, may be better suited than skin cells for making induced neurons to use in autism research. (see abstract below)

To study neurons associated with a disorder, researchers often revert skin cells from an individual with the disorder to a pluripotent state — from which they can become any cell type in the body. They then use these so-called induced pluripotent stem (iPS) cells to generate neurons in culture. A skin biopsy is painful and invasive, however.

Also, studies have shown that some epigenetic marks — modifications to DNA that influence which genes become active and when — may remain in these iPS cells. These may affect gene expression in the resulting neurons.

In the new study, researchers generated iPS cells from dental pulp, the living tissue inside of teeth, rather than from skin. Dental cells develop from the same set of early progenitors that neurons do, and so may be more similar to neurons than skin cells are.

Baby teeth are also easy to obtain, as children lose about 20 of them between the ages of 5 and 12 years. And for children with autism, even a visit to the doctor’s office to give blood (another source of iPS cells) may be difficult.

The researchers compared the genes expressed in neurons generated from dental pulp with those derived from two different skin samples. Overall, gene expression is similar among the cells, suggesting that they form essentially the same type of neurons. But the researchers found a subset of 63 genes that show statistically significant differences in expression.

In particular, HOX genes, which help direct brain development, are expressed at lower levels in the tooth-derived neurons than in the skin-derived ones. In contrast, some genes, such as FOXP2 and LHX2, which are expressed in the forebrain during development, are expressed at higher levels in the tooth-derived neurons. This latter group also includes a high proportion of genes implicated in schizophrenia.

The results suggest that tooth-derived neurons are well suited to study schizophrenia and related disorders such as autism, the researchers say.

 

Abstract from Plos one:

Induced pluripotent stem cell (iPSC) technology is providing an opportunity to study neuropsychiatric disorders through the capacity to grow patient-specific neurons in vitro. Skin fibroblasts obtained by biopsy have been the most reliable source of cells for reprogramming. However, using other somatic cells obtained by less invasive means would be ideal, especially in children with autism spectrum disorders (ASD) and other neurodevelopmental conditions. In addition to fibroblasts, iPSCs have been developed from cord blood, lymphocytes, hair keratinocytes, and dental pulp from deciduous teeth. Of these, dental pulp would be a good source for neurodevelopmental disorders in children because obtaining material is non-invasive. We investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on differentiated neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs). This is the first RNA-seq analysis comparing gene expression profiles in neurons derived from iPSCs made from different somatic cells. For the most part, gene expression profiles were quite similar with only 329 genes showing differential expression at a nominally significant p-value (p<0.05), of which 63 remained significant after correcting for genome-wide analysis (FDR <0.05). The most striking difference was the lower level of expression detected for numerous members of the all four HOX gene families in neurons derived from T-iPSCs. In addition, an increased level of expression was seen for several transcription factors expressed in the developing forebrain (FOXP2, OTX1, and LHX2, for example). Overall, pathway analysis revealed that differentially expressed genes that showed higher levels of expression in neurons derived from T-iPSCs were enriched for genes implicated in schizophrenia (SZ). The findings suggest that neurons derived from T-iPSCs are suitable for disease-modeling neuropsychiatric disorder and may have some advantages over those derived from F-iPSCs.

Tags: Dental Stem Cells, Research, Healthcare, Regenerative Medicine, Adult Stem Cells

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