DNA methylation patterns in human iPSC-derived sensory neuronal differentiation

Abstract

Sensory neurons of the peripheral nervous system are critical in health and disease. Sensory neurons derived from induced pluripotent stem (iPS) cells are now being used increasingly for in vitro models of neuropathy, pain, and neurotoxicity. DNA methylation is critical for neurodevelopment and has been implicated in many neuronal diseases, but has not been examined in iPS-derived sensory neurons. In order to better characterize the iPS-derived sensory neuron model, we have undertaken a genome-wide DNA methylation study on the cells from human iPS to iPS-derived sensory neurons during differentiation through reduced representation and bisulfite sequencing. We report decreasing DNA methylation with iPS-derived sensory neuronal differentiation that is reflected in increasing numbers and proportions of hypomethylated individual CpGs and regions, as well as lowered DNMT3b expression. Furthermore, genes with changes in DNA methylation near their TSS suggest key pathways that may be involved in iPS-derived sensory neuronal differentiation. These findings provide insights into sensory neuronal differentiation and can be used for further in vitro modelling of disease states.

METTL1-mediated m7G methylation maintains pluripotency in human stem cells and limits mesoderm differentiation and vascular development

“…The use of iPSCs can overcome the ethical issues of ESCs and is considered as a promising alternative for drug screening, disease modeling, and development of clinical treatments [27][28][29]. The molecular [8,11,30,31]. In our previous study, we reported that METTL1-deficient mouse ESCs display defective self-renewal and neural differentiation [13].…”

“…The molecular mechanisms underlying self-renewal and maintenance of pluripotency in iPSCs have been extensively studied. The stem cell genome undergoes reversible epigenetic modifications that regulate gene expression and dictate cell development and differentiation [ 8 , 11 , 30 , 31 ]. In our previous study, we reported that METTL1-deficient mouse ESCs display defective self-renewal and neural differentiation [ 13 ].…”

Recent advances for using human induced-pluripotent stem cells as pain-in-a-dish models of neuropathic pain

“…Furthermore, cell reprograming has been suggested to induce epigenetic changes, which constitute another important bias in pain studies (Thanuthanakhun et al, 2021). Specifically, differentiation has been shown to reduce DNA methylation (Ankam et al, 2019;Efrat, 2020). Our current inability to distinguish between differentiationinduced epigenetic modifications and the donor epigenome suggests that caution is needed in interpreting results of subject-specific iPSC-derived models.…”

New human in vitro co‐culture model of keratinocytes and sensory neurons like cells releasing substance P with an evaluation of the expression of ZIKV entry receptors: A potent opportunity to test Zika virus entry and to study Zika virus' infection in neurons?

“…Recent research allows the obtention of sensory neurons of human through the differentiation of induced pluripotent stem cells (iPS). [31][32][33][34][35][36][37][38] Hence, after validation of the model by induction of SP release we were interested in the expression of ZIKV entry receptors in keratinocytes and in human sensory nerve endings that are in the first line of external environment.…”

“…The limitation of these models is that sensory neurons were issued from animals. Recent research allows the obtention of sensory neurons of human through the differentiation of induced pluripotent stem cells (iPS) 31–38 …”