Consequences of ZNF292 deficiency for human cortical interneuron development

Human embryonic stem cell (hESC) models of ZNF292 deficiency were generated, including a KRAB-only control and two CRISPRi knockdown models (ZNF-G1 and ZNF-G2). These hESC models were used to derived MGE-like ventral telencephalic neural progenitors (day 15; D15) and cortical interneurons (day 30; D30). RNA-seq was conducted in these models to define transcriptional changes that result from ZNF292 deficiency during this process. For each time point, 4 biological replicates generated from independent differentiations of hESCs were used for comparison of transcriptomic differences between control (KRAB) and ZNF292 CRISPRi-mediated deficient (ZNF-G1 and ZNF-G2) progenitors and neurons.

本研究构建了ZNF292缺陷的人类胚胎干细胞（human embryonic stem cell, hESC）模型，涵盖仅含KRAB结构域的对照组与2种CRISPRi敲低模型（ZNF-G1、ZNF-G2）。利用该系列hESC模型，研究者诱导分化得到内侧神经节隆起（medial ganglionic eminence, MGE）样腹侧端脑神经前体细胞（分化第15天，D15）及皮层中间神经元（分化第30天，D30）。针对上述模型开展RNA测序（RNA sequencing, RNA-seq），以明确ZNF292缺陷在该分化进程中所引发的转录组变化。每个时间点均设置4个源自独立hESC分化实验的生物学重复，用于对比对照组（KRAB组）与ZNF292经CRISPRi介导的缺陷组（ZNF-G1、ZNF-G2）的前体细胞及神经元之间的转录组差异。