Comparative Chromatin Dynamics and Expression Profiles of Neural Progenitor and Definitive Endoderm Lineage Differentiation in Two Mammalian Species

One of the fundamental questions in developmental biology is how lineage specification is regulated and what regulatory transcription factors and signaling molecules are required. Lineage specification and differentiation are driven, at least in part, by chromatin remodeling causing changes in the accessibility of transcription factor binding sites. Changes in expression of required transcription factors are also important in the regulation of differentiation. To better understand which transcription factors drive differentiation and how these transcription factors differ between different species and differentiation lineages we differentiated ESCs into two different lineages, definitive endoderm and neural progenitors, and performed pooled RNA-seq and ATAC-seq in two different species, human and rat.发育生物学的核心基础问题之一，是阐明细胞谱系特化（lineage specification）的调控机制，以及该过程所需的调控型转录因子与信号分子。细胞谱系特化与分化至少部分由染色质重塑（chromatin remodeling）驱动，该过程可改变转录因子结合位点的染色质可及性。所需转录因子的表达变化，同样对分化调控具有重要意义。为了更清晰地解析驱动分化的转录因子，以及不同物种、不同分化谱系间此类转录因子的功能差异，我们将胚胎干细胞（embryonic stem cells, ESCs）诱导分化为定型内胚层（definitive endoderm）与神经前体细胞（neural progenitors）两种谱系，并在人类与大鼠两个物种中开展了混合池RNA测序（pooled RNA-seq）与ATAC测序（ATAC-seq）实验。