Transcription profiling by array of Gata3 knock-out mice

Transcriptome analysis on Gata3 conditional knock out murine hair follicles. Background. The transcription factor Gata3 is critically involved in epidermis and hair follicle differentiation. Yet, little is known about how Gata3 co-ordinates stem cell lineage determination in skin, which processes are mostly implicated and how Gata3 differentially regulates distinct cell populations within the hair follicle. Here, we describe a conditional Gata3-/- mouse (K14-Gata3-/-) in which Gata3 is specifically deleted in epidermis and hair follicles. Principal findings. K14-Gata3-/- mice show aberrant postnatal growth and development, delayed hair growth and maintenance, abnormal hair follicle organization and irregular pigmentation. After the first hair cycle, the germinative layer surrounding the dermal papilla was not restored; instead, proliferation was pronounced in basal epidermal cells. Transcriptome analysis of laser-dissected K14-Gata3-/- hair follicles as compared to wild type littermate controls, revealed mitosis, epithelial differentiation and the Notch, WNT and BMP signalling pathways to comprise significantly overrepresented processes. Conclusions. Subsequent elucidation of these pathways at the RNA and protein levels and physiologic endpoints shows that Gata3 integrates diverse signalling networks to regulate the balance between hair follicle and epidermal cell fates.Gata3条件性敲除小鼠毛囊的转录组学分析。 背景：转录因子Gata3在表皮与毛囊分化过程中发挥关键调控作用。然而，目前对于Gata3如何协调皮肤干细胞的谱系决定、涉及哪些核心生物学过程，以及Gata3如何差异化调控毛囊内不同细胞群的机制仍所知有限。 在此，我们构建了一种Gata3条件性敲除小鼠（K14-Gata3-/-），该模型中Gata3可在表皮与毛囊中特异性缺失。 主要发现：K14-Gata3-/-小鼠表现出异常的出生后生长发育表型，包括毛发生长与维持延迟、毛囊结构紊乱以及色素沉着异常。首次毛发周期结束后，真皮乳头周围的生发层未能正常修复；相反，基底表皮细胞的增殖活性显著增强。对激光捕获显微切割获取的K14-Gata3-/-毛囊与野生型同窝对照小鼠毛囊开展转录组分析，结果显示有丝分裂、上皮分化以及Notch、WNT、BMP信号通路均为显著富集的生物学过程。 结论：后续在RNA、蛋白质水平及生理终点层面对上述通路的解析表明，Gata3通过整合多种信号网络，调控毛囊细胞与表皮细胞的命运平衡。