An, B.; Tang, T.-C.; Zhang, Q.; Wang, T.; Gan, K.; Liu, K.; Liu, Y.; Wang, Y.; Shaw, W. M.; Liang, Q.; Wang, Y.; Lu, T. K.; Church, G. M.; Zhong, C.

Recent advancements in genetic engineering have provided diverse tools for artificially synthesizing population diversity in both prokaryotic and eukaryotic systems. However, accurately controlling the ratios of multiple cell types within a population derived from a single founder remains a significant challenge. In this study, we present a suite of recombinase-mediated genetic devices designed to achieve accurate population ratio control, enabling distinct functionalities to be distributed across multiple cell types. Key parameters influencing recombination efficiency were systematically evaluated, and data-driven models were developed to reliably predict binary differentiation outcomes. Using these devices, we implemented parallel and series circuit topologies to create user-defined, complex cell fate branching programs. These branching devices enabled the autonomous differentiation of precision fermentation consortia from a single founder strain optimizing cell-type ratios for applications such as pigmentation and cellulose degradation. Beyond biomanufacturing, we engineered multicellular aggregates with genetically encoded morphologies by coordinating self-organization through cell adhesion molecules (CAMs). Our work provides a comprehensive characterization of recombinase-based cell fate branching mechanisms and introduces a novel approach for the bottom-up, high-resolution constructing synthetic consortia and multicellular assemblies.