Ypsilanti Athéna R, Pattabiraman Kartik, Catta-Preta Rinaldo, Golonzhka Olga, Lindtner Susan, Tang Ke, Jones Ian R, Abnousi Armen, Juric Ivan, Hu Ming, Shen Yin, Dickel Diane E, Visel Axel, Pennachio Len A, Hawrylycz Michael, Thompson Carol L, Zeng Hongkui, Barozzi Iros, Nord Alex S, Rubenstein John L
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158;
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158.
Proc Natl Acad Sci U S A. 2021 Dec 21;118(51). doi: 10.1073/pnas.2024795118.
We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ventricular zone (VZ). We tested whether their cortical expression was altered in mutant mice with known patterning defects (, and ), which enabled us to define a cortical regionalization TF network (CRTFN). To identify genomic programming underlying this network, we performed TF ChIP-seq and chromatin-looping conformation to identify enhancer-gene interactions. To map enhancers involved in regional patterning of cortical progenitors, we performed assays for epigenomic marks and DNA accessibility in VZ cells purified from wild-type and patterning mutant mice. This integrated approach has identified a CRTFN and VZ enhancers involved in cortical regional patterning in the mouse.
我们发现了一个在放射状胶质干细胞中调节皮质区域模式形成的转录因子(TF)网络。通过筛选发育中小鼠皮质中数百种转录因子的表达,确定了38种在脑室区(VZ)呈梯度表达的转录因子。我们测试了它们在已知模式缺陷的突变小鼠( 和 )中的皮质表达是否发生改变,这使我们能够定义一个皮质区域化转录因子网络(CRTFN)。为了确定该网络背后的基因组编程,我们进行了转录因子染色质免疫沉淀测序(ChIP-seq)和染色质环构象分析以鉴定增强子-基因相互作用。为了绘制参与皮质祖细胞区域模式形成的增强子图谱,我们对从野生型和模式突变小鼠中纯化的VZ细胞进行了表观基因组标记和DNA可及性分析。这种综合方法已经确定了参与小鼠皮质区域模式形成的CRTFN和VZ增强子。