转化生长因子-β (TGFβ) 家族是一大类进化保守的细胞因子，其信号调控不同细胞环境下不同生命阶段的细胞命运决策。本文讨论了早期胚胎中的新发现，揭示了与我们对形态因子解释的初始理解相反，鲁棒的细胞命运指定可以由噪声组合的信号输入和广泛范围的信号水平产生。我们将这些证据与有关TGFβ家族信号在幼年和成年期间维持和稳态组织中的作用的新发现进行了比较，涵盖了骨骼、造血和免疫系统。通过这些比较，我们发现与鲁棒的发育系统相反，TGFβ家族信号的相对微小扰动在生命后期会产生有害效应，导致异常的细胞命运指定和疾病，例如癌症或先天性疾病。最后，我们重点介绍了针对信号功能失调的新策略，并讨论了如何从生物学的不同领域中获取知识以促进疾病中异常TGFβ家族信号的治疗方法的发展。© 2023. Springer Nature Limited.

The transforming growth factor-β (TGFβ) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in early embryos that reveal how, in contrast to our original understanding of morphogen interpretation, robust cell fate specification can originate from a noisy combination of signalling inputs and a broad range of signalling levels. We compare this evidence with novel findings on the roles of TGFβ family signalling in tissue maintenance and homeostasis during juvenile and adult life, spanning the skeletal, haemopoietic and immune systems. From these comparisons, it emerges that in contrast to robust developing systems, relatively small perturbations in TGFβ family signalling have detrimental effects at later stages in life, leading to aberrant cell fate specification and disease, for example in cancer or congenital disorders. Finally, we highlight novel strategies to target and amend dysfunction in signalling and discuss how gleaning knowledge from different fields of biology can help in the development of therapeutics for aberrant TGFβ family signalling in disease.© 2023. Springer Nature Limited.