Class C0 records a score of target features or observed screen outcomes. That score does not by itself settle representation, controllability, or evaluability. Boundary conditions.
Reprogram-Seq
Duan J, Li B, Bhakta M, Xie S, Zhou P, Munshi NV, Hon GC
2019 · Cell reports
Ectopic expression of transcription factors (TFs) can reprogram cell state.
Abstract
From the original paper, Cell reports · PubMed
Ectopic expression of transcription factors (TFs) can reprogram cell state. However, because of the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogramming performance. Reprogram-Seq leverages organ-specific cell-atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Focusing on the cardiac system, we perform Reprogram-Seq on MEFs using an undirected library of 48 cardiac factors and, separately, a directed library of 10 epicardial-related TFs. We identify a combination of three TFs, which efficiently reprogram MEFs to epicardial-like cells that are transcriptionally, molecularly, morphologically, and functionally similar to primary epicardial cells. Reprogram-Seq holds promise to accelerate the generation of specific cell types for regenerative medicine.
Summary
Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how Reprogram-Seq relates to the inverse-design framework of the review.
Why this class
Level 0 because the method scores features against a target/background contrast without modelling an intervention . The output is a ranked list of candidate identity determinants, not an intervention whose effect has been computed. Representation family is signature / state-matching. Cited in §3.1 of the review. Editorial rationale pending review by the maintainer.