The islets of Langerhans in the pancreas contain insulin-secreting β-cells and glucagon-secreting α-cells. Insulin and glucagon are hormones that cooperate to regulate the levels of glucose in blood. Destruction or dysfunction of β-cells leads to diabetes. Currently, no treatment can stop diabetes progression and its devastating vascular complications. Islet transplantation can often normalize blood glucose levels for several years and prevent the secondary complications of diabetes. However, organ donors are scarce, and alternative sources of islet cells are urgently needed. Stem-cell-derived cells are promising in this respect. Writing in Nature, Veres et al.1 map the molecular steps in the differentiation of stem cells into islet-like cells. The work will inform future efforts to produce islet cells for transplantation.
Human pluripotent stem cells can indefinitely self-renew and generate every cell type in the body. Therefore, immense efforts are ongoing to develop in vitro protocols to produce differentiating islet cells from stem cells2–5. An ideal protocol would promote the differentiation of stem cells into fully mature α-cells and β-cells, which would then be isolated, purified and reassembled into islet-like structures for transplantation into patients. To achieve such an ambitious goal, the differentiation programs of all islet cells, and the way in which islets are built, need to be fully understood.
Veres et al. assayed more than 100,000 cells at different time points during the differentiation of stem cells into pancreatic progenitor cells and then hormone-producing (endocrine) cells. Single-cell RNA sequencing (scRNA-seq) of cells sampled at every step of the differentiation process, followed by computational analyses, made it possible to identify cell types and to track their lineages through time. The authors therefore produced a fine-grained picture of how pancreatic progenitor cells develop into different lineages of differentiated cells (Fig. 1). Current approaches for producing specific differentiated cells from stem cells have variable efficiency, mostly because of cellular heterogeneity and a lack of knowledge about the molecular signalling factors required for the differentiation process. Therefore, the authors’ road map of in vitro islet-cell differentiation will inform the development of future differentiation protocols…
