Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny

Abstract

Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms.

The Role of Kv7.2 in Neurodevelopment: Insights and Gaps in Our Understanding

“…Because transcript c is the only curated long transcript that is missing exon 9 and 12, this suggests that transcript c is the longer transcript seen in self-renewal and NPC stage. Indeed, the expression of the short fetal transcript and transcript c in iPSCs and embryonic stem cells (ESCs) was confirmed in other studies, where they even demonstrated that KCNQ2 shows the highest expression of all ion channels (Wang et al, 2005;Jiang et al, 2010;Linta et al, 2013). It should, however, be noted that we cannot rule out that additional alternative transcripts without exon 9 and 12 exist that are not included in the curated RefSeq transcripts.…”

Expression of Pluripotency Genes in Chondrocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells

“…Linta and co-workers [ 18 ] investigated the gene expression profile of ion channels of keratinocyte-cell derived hiPSCs and keratinocytes, finding that the hiPSCs were characterized by specific an ion channel expression pattern. Additionally, the hiPSCs expressed a much higher number of ion channels compared to keratinocytes.…”

“…Additionally, the hiPSCs expressed a much higher number of ion channels compared to keratinocytes. Moreover, their differentiated progenitors (such as neurons and cardiomyocytes) also had a gene expression profile of various channel families and their subtypes that significantly differed from that of parental hiPSCs [ 18 ].…”

Stem Cells and Neuronal Differentiation

“…Even differentiated Parkinson patient-derived iPSCs grew in the adult rodent brain and reduced motor asymmetry in Parkinsonian rats [97,98]. A recent detailed gene expression microarray study indicated that expression of ion channels such as voltage-gated Ca 2C , Na C , and K C channels, ionotropic neurotransmitter receptors, and ionotropic purinergic receptors is distinctly upregulated in the differentiated progeny of iPSCs in comparison to the starting cell type [99]. Furthermore, electrophysiological recordings and morphological analysis showed that the grafted cells had attained neuronal integration and synaptic activity.…”