Cindy Boer

54 | Chapter 1.2 subpopulations in cartilage[140]. Because of the high sensitivity of single‐cell genomics, attention must be put into experimental setup and execution of this technology. Careful handling and processing of cells is critical to preserve the native epigenetic and expression profile; only then mean- ingful analysis and conclusions can be drawn. This is especially important for the study of skeletal cells because their natural habitat is normally deeply embedded in the ex- tracellular matrix and getting a single‐cell solution from cartilage or bone is not trivial. A new field of epigenetic regulation is epi‐transcriptomics[141]. These are RNA modifications that represent a novel layer of regulation of gene expression. Early re- ports show the existence of many different dynamic RNA modifications. The role of these RNA modifications in regulating gene expression is largely unexplored, but recent evidence suggests that these RNA modifications are key switches for RNA metabolism. It took more than 1,500 years to evolve from Ptolomeo's map to good world maps. The map of the human epigenome is probably much more complex. Fortunately, technical advances allow us to be optimistic and not expect such a long time for the final drawing. However, building the maps of the human epigenome and specifically of hu- man skeletal cells, as well as the tracks to be travelled to get into the core mechanisms driving the move from healthy bones and joints toward disease, is still a formidable work. Intensive collaboration of multiple research groups working together is a must to accomplish such a daunting task. Previous experience in the genetic field shows that it may be difficult to do, but it is feasible. A new world of hope for millions of patients is ahead. Disclosures All authors state that they have no conflicts of interest. Acknowledgments Authors’ studies were supported by grants from Instituto de Salud Carlos III to JAR (PI16/915; which may be co‐funded by EU funds) and Reuma Nederland (16‐1‐404). Authors’ roles: JBJM, CGB, LLD and JAR contributed to conception, writing and revision of the manuscript.