AI Article Synopsis
- Cell type specification in pancreatic development relies on a complex transcriptional and epigenetic network, with many roles of transcription factors still unclear outside of mouse studies.
- Alternative models like in vitro differentiation of human pluripotent stem cells can help translate findings to human development.
- Analysis of RNA, ChIP, and ATAC-sequencing data highlighted ONECUT1 as a key regulator in pancreatic progenitors and its involvement in later endocrine specification, offering insights for future research on human development and related diseases.
Article Abstract
Cell type specification during pancreatic development is tightly controlled by a transcriptional and epigenetic network. The precise role of most transcription factors, however, has been only described in mice. To convey such concepts to human pancreatic development, alternative model systems such as pancreatic in vitro differentiation of human pluripotent stem cells can be employed. Here, we analyzed stage-specific RNA-, ChIP-, and ATAC-sequencing data to dissect transcriptional and regulatory mechanisms during pancreatic development. Transcriptome and open chromatin maps of pancreatic differentiation from human pluripotent stem cells provide a stage-specific pattern of known pancreatic transcription factors and indicate ONECUT1 as a crucial fate regulator in pancreas progenitors. Moreover, our data suggest that ONECUT1 is also involved in preparing pancreatic progenitors for later endocrine specification. The dissection of the transcriptional and regulatory circuitry revealed an important role for ONECUT1 within such network and will serve as resource to study human development and disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599846 | PMC |
| http://dx.doi.org/10.1038/s42003-021-02818-3 | DOI Listing |
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