 A hallmark of multicellularity is the capacity to have different specialized cell types within the same body, which is called spatial cell differentiation. This division of labor allows the organism to perform different tasks at the same time, something that only multicellular organisms can do. In animals, this special distribution of cell types is defined by a specific profile of protein abundance and by their regulation through phosphorylation, which are known as proteome and phosphoproteome profiles respectively. It is known that many essential genes involved in animal multicellularity and protein regulation first evolved in a unicellular context. But how and when did the mechanisms that regulate spatial cell differentiation evolve? To understand this transition, researchers at the Multicell Genome Lab in the Proteomics Unit analyzed the proteome and phosphoproteome of a close unicellular relative of animals, the amoeba capsis pora azarizaki. This protist is an ideal candidate to understand the origin of cell differentiation, for three main reasons. First, it holds a key phylogenetic position as a close relative of animals. Second, it has a rich repertoire of genes involved in multicellular functions, such as cell differentiation and cell signaling. Third, Capsis Pora's life cycle comprises three different stages, with each stage involving a different cell type. This allowed the researchers to analyze the protein's activity across three different cell types. One stage consists of individual amoebas with cell protrusions known as phylopodia, used to attach to the substrate. This can be followed by a cystic stage without cell protrusions, or by an aggregative stage in which the amoebas gather together and form a multicellular structure. The first observation was that, as in animals, the number and types of proteins in this organism is specific for each life stage. In other words, each of Capsis Pora's life stages has a different cell type and also a different and specific proteome profile. Moreover, the phosphoproteum analysis revealed that many proteins are also regulated by phosphorylation in a cell type specific manner. That is, some proteins are phosphorylated in one cell type, but not in others, again as it happens in animals. Thus, Capsis Pora and animals share the same mechanisms to differentiate cells by changing the protein profile and phosphorylation. However, Capsis Pora uses these mechanisms to differentiate cells during the transition to different cell stages of its life cycle, known as temporal cell differentiation, while animals not only differentiate cells in time but also in space, spatial cell differentiation. Based on these results, the researchers hypothesized that the mechanisms of spatial cell differentiation were already present in the unicellular ancestor of animals. However, these mechanisms were probably used to differentiate cell types across life stages in a temporal manner, as Capsis Pora does, and were later recycled in animals to spatially differentiate cells within a single multicellular body. Therefore, these mechanisms might constitute the molecular basis for the transition from temporal to spatial cell differentiation, which helped shape multicellularity in animals.