Tcf21, a member of the basic helix-loop-helix (bHLH) transcription factors, plays a crucial role in various biological processes. It mediates cell fate and differentiation, influencing organogenesis, epithelial-mesenchymal transition (EMT), cell cycle, and more. It is involved in pathways related to cell survival, proliferation, and in the context of disease, invasion and metastasis [4,5]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In the context of colorectal cancer, Tcf21high pericyte subpopulation was found to promote liver metastasis. Tcf21 in tumor pericytes (TPCs) increased perivascular extracellular matrix (ECM) stiffness, collagen rearrangement, and basement membrane degradation, creating a metastatic microenvironment. Depletion of Tcf21 in TPCs using Tcf21-conditional knockout mice mitigated perivascular ECM remodelling and colorectal cancer liver metastasis (CRCLM) [1]. In vascular smooth muscle cells (SMCs), SMC-specific knockout of Tcf21 inhibited SMC phenotypic modulation in mice, leading to fewer fibromyocytes in atherosclerotic lesions, suggesting a protective role in coronary artery disease (CAD) [2]. In epicardium-derived cells, loss of Tcf21 function caused increased myofibroblast differentiation, while forced overexpression suppressed transforming growth factor-β signalling and myofibroblast differentiation [3].

In conclusion, Tcf21 is essential in multiple biological processes. Studies using KO/CKO mouse models have revealed its significance in diseases like colorectal cancer, coronary artery disease, and myocardial fibrosis. These models have provided insights into how Tcf21 functions in specific cell types and contributes to disease-related processes, which may help in developing diagnostic markers and therapeutic targets.