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Control of ESC-to-NPC Transition by TGFβ/BMP Signaling

Extrinsic cell signaling is transmitted through intracellular proteins that converge on gene transcription to steer cell fate and differentiation. The study of the roles of such top‐down pathways during development has historically employed single‐component perturbations with read‐out time points covering multiple developmental stages. A new study from the labs of Ruben Dries and Danny Huylebroeck (Erasmus University Medical Center, Rotterdam, Netherlands) systematically profiled multiple components of the TGFβ/BMP pathway using time‐series, perturbations, and single‐cell analysis during the differentiation of mouse embryonic stem cells (mESCs) to neural progenitor cells  (NPCs). The authors now advise that this pathway should be considered an intricate intra‐dependent network of individual components with considerable cell‐stage specificity. Hence, interpretation of the consequences of single‐gene perturbation or knockout in lineage‐progressing cells should occur with caution regarding stage and transition. For more on this concept, see STEM CELLS now!