6/ Applying these insights to stem cell differentiation, we show that manipulating P-body assembly or specific microRNA activity can direct pluripotent stem cells toward totipotency or the germ-cell lineage.

5/ What drives the selective sequestration of mRNAs in P-bodies? We found that certain cell-type–specific microRNAs are enriched in P-bodies and modulate RNA sequestration. Disrupting microRNA–target interactions prevents the corresponding mRNAs from being sequestered.

4/ Dissolving P-bodies in mouse naïve ESCs increased ribosome occupancy of P-body–enriched RNAs, including 2C transcripts, triggering reversion to a 2C-like state. This shows that releasing RNAs from P-bodies enables their translation and drives cell fate transitions.

3/ Surprisingly, P-body contents don't simply reflect current gene expression but are enriched with transcripts from the prior developmental stage. For example, in human naïve pluripotent ESCs, P-bodies sequester RNAs linked to the totipotent 8-cell embryonic stage.

2/ Using fluorescence-activated particle sorting, we profiled P-body contents across developmental stages and vertebrate species. P-body composition is cell-type specific, and the sequestered transcripts are translationally repressed.

5/ Recent technological advancements have powered these studies, enabling answers to previously unanswerable questions (Fig. 4). Despite this progress, critical evaluation of the evidence concerning condensate properties is essential to understand their role in immune cell fate.

4/ Conversely, dysregulation of condensates has been linked to deleterious immune cell fates, including impaired function, autoimmunity, aging, and malignant transformation (Fig. 3).

3/ Recent studies have implicated condensates in the transcriptional and post-transcriptional processes that drive proper immune cell fates, from the level of hematopoietic stem cells to innate and adaptive immune cells (Fig. 2).

2/ Condensates are diverse, membraneless assemblies of nucleic acids and proteins (Fig. 1). They are thought to enable temporally precise control of gene expression by concentrating or segregating components of the gene regulatory machinery and their targets.