Yoshiki Sasai (1962–2014) Stem-Cell Biologist Who Decoded Signals in Embryos

COMMENT OBITUARY Yoshiki Sasai (1962–2014) Stem-cell biologist who decoded signals in embryos.

ow does a fertilized egg — a single which the brain’s cerebral cortex arises. By medicine. He thought that it could be cell — produce the myriad special carefully adding growth factors, he coaxed pushed even further, thinking of ways to ized cells that assemble into three- the organoids into forming the front or the generate multiple brain structures in vitro Hdimensional tissues and functioning back of the cortex. These advances provide that could become interconnected. organs? This fundamental secret has capti powerful tools for understanding healthy Sasai obtained his MD in 1986 and his vated generations of embryologists. Using and aberrant human brain development. PhD in 1993 from Kyoto University, where creative culture conditions and unmatched The methods that he developed may one he trained as a molecular biologist in the insight into the action of biological signals day be used to make replacement cells to laboratory of neuroscientist Shigetada that govern tissue development, Yoshiki treat currently uncurable diseases. Nakanishi. He then went to the Univer Sasai found ways to mimic these sity of California, Los Angeles, and mysterious processes in the labora worked with embryologist Edward tory. He leaves a legacy of remark De Robertis to discover chordin, able discoveries that expand the one of the key early inducers in frontiers of stem-cell research and the formation of the nervous sys tissue regeneration. tem. In 1996, Sasai moved back to Yoshiki struck me as a happy Kyoto University, where he began scientist. He spoke softly and with a his extraordinary work mimicking unique smile as he described Japanese embryonic development in a dish. traditions or revealed his astonishing He moved to RIKEN in 2000. findings. My first experience of his Given the pride that Yoshiki felt for OF ARTURO ALVAREZ-BUYLLA COURTESY pride and passion came during a long the work he was doing in his home walk on Japan’s Rokko Mountain in country, his enjoyment of and devo 2008. We looked over the splendour tion to good science, his family, and of Kobe and the reclaimed island life in general, I was shocked to learn where his institute, the RIKEN Center that on 5 August my admired col for Developmental Biology, lay. The league and dear friend had taken his sight brought that smile to his face. As own life. Clearly, his mental state took he taught me the art of ninja walking, a very heavy blow from the onslaught recounted the local thousand-year- of media attention and the months of old methods used to make sake, and allegations surrounding two Nature dissected the etiquette of Japanese papers published in January from the bathing, he explained some of his laboratory of Haruko Obokata, on incredible scientific discoveries. Sasai amazed the stem-cell community the generation of stimulus-triggered acqui Sasai was a master at deciphering the with time-lapse videos showing human sition of pluripotency (STAP). Laboratories code by which cells learn their place in a and mouse ES cells turning into optic around the world were unable to reproduce developing embryo. He tested this code vesicles, the precursors of eyes. He dem the findings, and after serious problems on cultures of embryonic stem (ES) cells onstrated that these go on to form an were found with the studies, the papers were derived from early-stage embryos, and optic cup and all the major cell types in retracted in July. Although the work was not instructed these unspecialized cells into the retina. Sasai’s laboratory inferred the a direct product of his laboratory, Sasai was becoming specific types of neuron. He basic principles of how eyes form from self- a co-author of the papers. In June, he wrote made nerve cells found in different parts directed cell assembly, gaining insights into to me expressing his deep concerns about of the forebrain by varying concentrations a process that is difficult to monitor and the worsening STAP situation in Japan. of morphogens, molecules that guide the manipulate in developing animals. When Yoshiki’s career was full of insights that patterning of tissues. Sasai’s laboratory I visited his laboratory in February, Sasai prompted the unique smile that we will developed the first methods to make inhibi shared recent work indicating how these greatly miss. I hope that his realized and tory interneurons, which hold promise for optic cups acquired polarity, in which unrealized ideas inspire the next genera brain repair. He also discovered a simple set individual cells take on different proper tions of scientists to follow his solid legacy of cues to make the brain’s hypothalamic ties according to their position in a larger of research. It is a true tragedy that the scien neurons and pituitary cells, important for structure. This trait is crucial for neural tific community is left without this forward several bodily functions. connectivity and vision. thinker. ■ Sasai instructed both mouse and human Sasai’s work deriving cortical, visual and ES cells to become cortical neurons, the pituitary tissues demonstrated that com Arturo Alvarez-Buylla is professor of type that expanded markedly during the plex, highly organized structures could be neurological surgery at the University evolution of the human brain. Remarkably, made from isolated human ES cells. The of California, San Francisco, USA. He his ES-cell-derived cortical cells assembled work broke new ground in understand collaborated with Yoshiki Sasai between into floating, three-dimensional orga ing tissue and organ formation, model 2008 and 2014. noids similar to the embryonic organ from ling disease and advancing regenerative e-mail: [email protected]