Black Family Stem Cell Institute, The Tisch Cancer Institute, Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Cell Rep. 2019 Jul 2;28(1):257-266.e5. doi: 10.1016/j.celrep.2019.06.011.
How tissue patterns are formed and maintained are fundamental questions. The murine tongue epithelium, a paradigm for tissue patterning, consists of an array of specialized fungiform papillae structures that harbor taste cells. The formation of fungiform papillae is preceded by pronounced spatial changes in gene expression, in which taste cell genes such as Shh, initially diffused in lingual epithelial progenitors, become restricted to taste cells when their specification progresses. However, the requirement of spatial restriction of taste cell gene expression for patterning and formation of fungiform papillae is unknown. Here, we show that a chromatin regulator, Polycomb repressive complex (PRC) 1, is required for proper maintenance of fungiform papillae by repressing Shh and preventing ectopic SHH signaling in non-taste cells. Ablation of SHH signaling in PRC1-null non-taste cells rescues the maintenance of taste cells. Altogether, our studies exemplify how epigenetic regulation establishes spatial gene expression patterns necessary for specialized niche structures.
组织模式是如何形成和维持的是基本问题。鼠舌上皮组织是组织模式的范例,它由一系列专门的菌状乳头结构组成,这些结构包含味觉细胞。菌状乳头的形成之前是基因表达的显著空间变化,在此期间,Shh 等味觉细胞基因最初在舌上皮祖细胞中扩散,当它们的特化进展时,这些基因会被限制在味觉细胞中。然而,味觉细胞基因表达的空间限制对于菌状乳头的模式形成和形成是未知的。在这里,我们表明,染色质调节剂多梳抑制复合物 (PRC) 1 通过抑制 Shh 和防止非味觉细胞中的异位 SHH 信号传导来维持菌状乳头的正常发育。PRC1 缺失的非味觉细胞中 SHH 信号传导的缺失可挽救味觉细胞的维持。总的来说,我们的研究例证了表观遗传调控如何建立专门生态位结构所需的空间基因表达模式。