Cell Fate Determination and Lineage Tracing: Technological Evolution and Multidimensional Applications.

Cell fate determination is a fundamental process in multicellular development. In multicellular organisms, cells display plasticity in their fate, allowing them to revert to prior states or adopt alternative differentiation pathways, thereby altering their identity and functional specialization in response to specific stimuli. Investigating cell fate determination and its plasticity enhances our understanding of organ development, tissue homeostasis, and disease pathogenesis and progression, providing novel insights into regenerative medicine strategies. Lineage tracing technologies have fundamentally revolutionized this understanding of cell fate dynamics by enabling the identification and tracking of cells and their progeny in vivo. These technologies have progressed significantly, from the direct observation and manual annotation of cell lineage trees to complex recombinase-mediated genetic labeling techniques. With the advent of sequencing technologies, the resolution and scale of lineage tracing have also developed toward the single-cell level in individual organisms. Furthermore, lineage tracing is increasingly expanding to investigate how the tissue microenvironment influences cell fate decisions. Here, the evolution of lineage tracing technologies is introduced and their applications in cell fate determinations across development, regeneration, and diseases contexts.