A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas
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A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas. / Yang, Xiaodun; Raum, Jeffrey C.; Kim, Junil; Yu, Reynold; Yang, Juxiang; Rice, Gabriella; Li, Changhong; Won, Kyoung-Jae; Stanescu, Diana E.; Stoffers, Doris A.
I: Development, Bind 149, Nr. 13, 200432, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas
AU - Yang, Xiaodun
AU - Raum, Jeffrey C.
AU - Kim, Junil
AU - Yu, Reynold
AU - Yang, Juxiang
AU - Rice, Gabriella
AU - Li, Changhong
AU - Won, Kyoung-Jae
AU - Stanescu, Diana E.
AU - Stoffers, Doris A.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Pancreas development
KW - ChIP-seq
KW - Single-cell RNA-seq
KW - Mouse
KW - Human
KW - PDX1 cistrome
KW - BETA-CELLS
KW - INSULIN-SECRETION
KW - EARLY-ONSET
KW - GENE
KW - DIFFERENTIATION
KW - MAINTAINS
KW - ACTIVATION
KW - EXOCRINE
KW - IDENTITY
KW - ALPHA
U2 - 10.1242/dev.200432
DO - 10.1242/dev.200432
M3 - Journal article
C2 - 35708349
VL - 149
JO - Development
JF - Development
SN - 0950-1991
IS - 13
M1 - 200432
ER -
ID: 317368993