Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Development. 2022 Jul 1;149(13). doi: 10.1242/dev.200432. Epub 2022 Jun 29.
Pancreatic and duodenal homeobox 1 (PDX1) is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 binding in human or mouse developing pancreas have not been examined. To address this knowledge gap, we performed PDX1 ChIP-seq and single-cell RNA-seq using fetal human pancreata. We integrated our datasets with published datasets and revealed the dynamics of PDX1 binding and potential cell lineage-specific PDX1-bound genes in the pancreas from fetal to adult stages. We identified a core set of developmentally conserved PDX1-bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known dramatic changes in PDX1 function and expression, we found that PDX1-bound genes are largely conserved from embryonic to adult stages. This points towards a dual role of PDX1 in regulating the expression of its targets at different ages, dependent on other functionally congruent or directly interacting partners. We also showed that PDX1 binding is largely conserved in mouse pancreas. Together, our study reveals PDX1 targets in the developing pancreas in vivo and provides an essential resource for future studies on pancreas development.
胰腺十二指肠同源盒 1（PDX1）对于胰腺器官发生至关重要，但尚未研究人类或小鼠发育中的胰腺中 PDX1 结合的动态变化。为了解决这一知识空白，我们使用胎儿人胰腺进行了 PDX1 ChIP-seq 和单细胞 RNA-seq。我们将我们的数据集与已发表的数据集进行了整合，揭示了 PDX1 结合的动力学以及胰腺从胎儿到成年阶段潜在的细胞谱系特异性 PDX1 结合基因。我们确定了一组核心的发育保守的 PDX1 结合基因，这些基因揭示了 PDX1 在胰腺发育中的广泛多方面作用。尽管 PDX1 功能和表达的明显变化众所周知，但我们发现从胚胎到成年阶段，PDX1 结合基因在很大程度上是保守的。这表明 PDX1 在调节其靶基因的表达方面具有双重作用，这取决于其他功能一致或直接相互作用的伙伴。我们还表明，PDX1 结合在小鼠胰腺中也很大程度上是保守的。总之，我们的研究揭示了体内发育中胰腺的 PDX1 靶标，并为未来的胰腺发育研究提供了重要资源。
