By Toby Lanser
Over the years, stem cell research has gained traction with its potential to regenerate damaged tissues, organs, or even full limbs. Stem cells are primitive cells that differentiate into specific cell types that make up all the tissues in the body. Researchers have been able to expose stem cells to a concoction of different cellular signals in order to differentiate them into specialized cell types. Through the differentiation of single stem cells, scientists are now trying to grow full functioning organs in labs to understand an organ’s development and hopefully to use functioning ones as transplants into patients with failing systems. In a paper published in the November 2018 issue of the journal Cell Stem Cell, scientists from Washington University School of Medicine in St Louis, one of the world’s leading medical schools, investigated the development of stem cells that they hoped would differentiate into subpopulations of kidney cells, but there was a surprise in store when they sequenced the genome of all the cells being cultured.
Some of the nascent kidney cells had gone rouge and started to develop the genetic expression unique to brain cells! What had happened? Was this some kind of organic Frankenstein, where lab-grown cells began to literally develop a brain of its own? What had initially started out as a standard differentiation of stem cells turned into an experiment that could serve as the foundation for future studies to shed light the signaling pathways required to make ultra-specific cell types.
Lead by researcher Dr. Haojia Wuand along with principal investigator Dr. Benjamin Humphreys, the team set out to compare organoids (miniature, stem cell derived organs) based on well-established differentiation protocols with actual human tissue of the same type. This comparison is important because if the organoid is not similar to that of naturally developed tissue, it could prove disastrous for the future of stem cell medicine, as well as all previous research based on these protocols. If the lab-grown organs are in fact similar, however, it would be reasonable to move forward with experiments geared towards transplantation or regeneration of damaged tissue. Furthermore, if the results proved an accurate supplement to human tissue, organoids could become a valuable tool in studying diseases specific to certain cell types and tissues.
Everything went as planned for Wuand until the team checked the genomic expression of their cells. To their surprise, about 10-20 percent of the cell population did not express the genes usually associated with kidneys, instead, they aligned closely with that of neurons. Relative to their initial goal, this was not good news. However, the team’s results did elucidate the what could be a similarity in signaling required to make different subtypes kidney cells and neurons. These results show the beauty of biology in how we have evolved such sensitive receptors in our primitive stem cells meaning that a slight change in signaling can lead to drastically different cell types.
Wu, H., Uchimura, K., Donnelly, E., Kirita, Y., Morris, S., & Humphreys, B. (2018). Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell Transcriptomics. Cell Stem Cell. doi: 10.1016/j.stem.2018.10.010