New research has shown the importance of the Id1 gene in controlling transition between cell states during development of the mouse embryo.
During early development of an embryo, pluripotent cells have the capacity to differentiate to become any other cell type in the body. Naïve pluripotent cells choose their fate according to the signals they receive from their local environment. The ability to respond or to or to ignore signals must be tightly coordinated at different stages of development in order to ensure that their fate is not misdirected. This becomes particularly important when the same signal is responsible for different cell fate decisions at different times.
Early development of the embryo is characterised by a change in cell identity from naïve to primed cells. The signals given off by cell signalling protein Fibroblast Growth Factor (FGF) result in different outcomes depending on whether they are received by naïve or primed cells. This new study explains that, Bone Morphogenic Protein target gene Id1 suppresses FGF and stabilizes cell identity specifically during the transition phase between naive and primed states.
Cell identity is controlled by transcription factors (TFs) such as Nanog and Nodal which control which genes are switched on and off. Nanog supports pluripotency in naive cells, while Nodal supports pluripotency in primed cells. If the handover from Nanog to Nodal does not proceed seamlessly this raises the possibility of abnormal cell differentiation.
The research shows that Id1 acts as a “sensor” to detect when cells have lost Nanog expression but have not yet acquired Nodal activity. In this case, Id1 subdues FGF in order to protect these cells from abnormal differentiation. Once a primed state has been achieved Nodal suppresses Id1 expression and so permits FGF activity to rise to help sustain pluripotency. In this way Id1 can sense delays and adjust the timing of differentiation.
CRM Group Leader Dr Sally Lowell, who led the study team, said:
“Pluripotent cells must maintain their potency as they transit through early development, but the signals they need to support potency don't always appear on cue. This paper reports how cells detect such problems and adapt to them".
This work was supported by funding from the Wellcome Trust. This paper is published in Developmental Cell: 50, 1–16, 19 August 2019.