Tcf15, encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2, is a transcription factor with diverse functions [5]. It is involved in pathways related to hematopoiesis, peripheral nerve development, pluripotent cell differentiation, and fatty acid uptake in the heart [1,2,3,4]. Its functions are crucial for normal development and physiological processes in organisms, and genetic models are valuable for studying its roles.

In hematopoiesis, in vivo CRISPR screening showed that Tcf15 is required and sufficient to drive hematopoietic stem cell (HSC) quiescence and long-term self-renewal, and its in situ expression labels the most primitive subset of true multipotent HSCs [1]. In zebrafish, targeted loss of tcf15 via CRISPR-Cas9 genome editing led to peripheral nerve patterning abnormalities, suggesting it non-cell-autonomously promotes peripheral nerve patterning through muscle-derived extracellular cues [2]. An Id-resistant form of Tcf15 rapidly downregulates Nanog and accelerates somatic lineage commitment in embryonic stem cells [3]. In heart capillary endothelial cells, Meox2/Tcf15 heterodimers mediate fatty acid uptake, and combined Meox2 and Tcf15 haplodeficiency impaired fatty acid uptake in heart ECs and reduced fatty acid transfer to cardiomyocytes, resulting in impaired cardiac contractility in the long term [4].

In conclusion, Tcf15 plays essential roles in multiple biological processes such as hematopoiesis, peripheral nerve development, pluripotent cell differentiation, and cardiac fatty acid uptake. Model-based research, especially gene knockout-related studies, has been instrumental in revealing these functions. Understanding Tcf15's functions can potentially contribute to the study of related diseases like hematological malignancies and cardiac dysfunction [1,2,3,4].