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bioRxiv · 10.1101/2021.02.28.433241

PDX1 directs a core developmentally and evolutionarily conserved gene program in the pancreatic islet

Yang, X.·Raum, J. C.·Kim, J.·Yu, R.·Yang, J.·Rice, G.·Li, C.·Won, K.-J.·Stoffers, D. A.·Stanescu, D. E.
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Abstract

Pancreatic and duodenal homeobox 1 (PDX1) is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 targets in mouse or human pancreas development have not been examined. We integrated the PDX1 cistrome with cell lineage-specific gene expression in both mouse and human developing pancreas. We identified a core set of developmentally and evolutionarily 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 showed that PDX1 binding is largely stable from embryonic pancreas to adult islet. This may point towards a dual role of PDX1, activating or repressing the expression of its targets at different ages, dependent on other functionally-congruent or directly-interacting partners. Our work also suggests that PDX1 functions not only in initiating pancreas differentiation, but also as a potential keepsake of the progenitor program in the adult beta cells.

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Yang, X., Raum, J. C., Kim, J., Yu, R., Yang, J., Rice, G., Li, C., Won, K.-J., Stoffers, D. A., Stanescu, D. E.. 2021-02-28. PDX1 directs a core developmentally and evolutionarily conserved gene program in the pancreatic islet. https://doi.org/10.1101/2021.02.28.433241

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