Zfp536, a gene with currently no widely-known common aliases, is involved in multiple biological processes. It has been implicated in cell lineage differentiation, such as in dermal fibroblast development where it is a putative key driver gene for the papillary fibroblast trajectory [1]. It also seems to play a role in the development of the cerebral cortex, with a sense lncRNA SenZfp536 cis-regulating Zfp536 and affecting the proliferation of cortical neural progenitor cells [2]. In tooth initiation, Zfp536 is among the transcription factors found near the Sox2:Tfap2a/Tfap2b interface in the mandibular epithelium, suggesting its involvement in transcriptional regulatory networks controlling tooth development [3]. Additionally, it has been identified as a candidate gene for obesity through whole-genome sequencing of mouse lines divergently selected for fatness and leanness [4].

In the generation of oligodendroglial cells, forced expression of Zfp536 along with Sox10 and Olig2 can reprogram mouse and rat fibroblasts into induced oligodendrocyte precursor cells (iOPCs) with morphologies and gene expression signatures resembling primary OPCs [6]. Different combinations of transcription factors show differential efficiency in reprogramming iOPCs from mouse and rat fibroblasts, with the combination of Olig2, Sox10, and Zfp536 being more effective in rat fibroblasts [5]. Moreover, drugs can enhance the myelinating capacities of iOPCs generated using Zfp536-based conversion [7]. In the context of lens development, shRNA-mediated knockdown of Pax6, a key regulator of lens formation, leads to down-regulation of Zfp536, accompanied by changes in histone H3K4 methylation at enhancers and promoters [8].

In summary, Zfp536 is involved in diverse biological processes including cell lineage differentiation, neural progenitor cell proliferation, tooth development, and potentially obesity. Its role in generating oligodendroglial cells through direct lineage conversion has implications for disease modeling and regenerative medicine. The study of Zfp536 using gene-knockdown and other model-based research methods helps in understanding these biological processes and provides insights into potential therapeutic strategies related to demyelinating diseases and other conditions [1-4, 6-10].