Stat5a, short for Signal Transducer and Activator of Transcription 5A, is a transcription factor that mediates signals for various cytokines. It is involved in crucial cellular functions such as proliferation, differentiation, and apoptosis, playing a significant role in processes like hematopoiesis, immunoregulation, and cancer development. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions [1,2,3,4,5,6,7,8].

In hematopoiesis, while Stat5a and Stat5b were once considered largely redundant, recent evidence shows that they have distinct functions, with Stat5b having a more prominent role in normal and malignant hematopoiesis [1]. In gastric cancer, increased p-Stat5a levels are associated with tumor invasion and poor prognosis, and Stat5a promotes cancer cell proliferation by upregulating CD44 expression [2]. In neuroendocrine prostate cancer, loss of androgen receptor leads to increased PAX6 expression, which drives neuroendocrine phenotypes through the MET/Stat5a signaling pathway [3]. In chondrocyte hypertrophic differentiation, Stat5a promotes Col10a1 gene expression, possibly via interaction with the Col10a1 cis-enhancer [4]. In diabetic nephropathy, Stat5a directly regulates ELTD1 transcription, participating in high-glucose-mediated endothelial-to-mesenchymal transition (EndMT) [5]. In atherosclerosis, GM-CSF-activated Stat5a regulates macrophage functions and inflammation [6]. In breast cancer, Stat5a confers doxorubicin resistance by regulating ABCB1 [7].

In conclusion, Stat5a is essential in multiple biological processes and disease conditions. Model-based research, particularly KO/CKO mouse models, has revealed its diverse roles in areas such as hematopoiesis, cancer progression, and organ-specific pathologies like diabetic nephropathy and atherosclerosis. Understanding Stat5a functions provides insights into disease mechanisms and potential therapeutic targets.