A spatial transcriptomic analysis of key human sensory neurons is presented in Science Translational Medicine this week, uncovering potential new drug targets for pain management. Despite the significant medical problem pain represents, there has been little progress translating preclinical work on peripheral pain mechanisms, which has largely been done in rodents, into effective pain therapeutics. One explanation for this failure is that important species differences in sensory neuron molecular phenotypes may exist between mice and humans, an idea partially supported by bulk RNA sequencing experiments. In the study, a team led by scientists from the University of Texas at Dallas used spatial transcriptomics to molecularly characterize transcriptomes of single dorsal root ganglia, which contain nociceptors. They compared the results to similar analyses in rodents and nonhuman primates, identifying important gender- and species-dependent differences, as well as potential pharmacological targets. "This comprehensive spatial characterization of human nociceptors might open the door to development of better treatments for acute and chronic pain disorders," the authors write.
A study using single-cell RNA sequencing to map the differentiation from induced pluripotent stem cells (iPSCs) to platelet-producing megakaryocytes in vitro is published by a University of Cambridge team in Science Advances this week. The scientists previously developed a system for producing megakaryocytes from pluripotent stem cells for the treatment of platelet deficiency. These cultures can be maintained for more than 100 days, implying culture renewal by megakaryocyte progenitors (MKPs), but it was not clear whether the MKP state in vitro mirrors the state in vivo. Additionally, MKPs cannot be purified using conventional surface markers. In their latest report, the investigators used scRNA-seq to map megakaryocyte differentiation at high resolution from iPSCs to their mature state, generating an overview of the cell fates acquired during differentiation and demonstrating that their system accurately generates MKPs and erythroid progenitors that mirror their in vivo counterparts. They also identify five surface markers that reproducibly purify MKPs, providing insight into their transcriptional and epigenetic profiles. The study's authors note that their methodology can be applied to other stem cell differentiation systems and allow for the identification of specific surface markers for cellular products.