Control of Cell Identity in Pancreas Development and Regeneration

Stanger, Ben Z.; Hebrok, Matthias

doi:10.1053/j.gastro.2013.01.074

Cited by 134 publications

(92 citation statements)

References 80 publications

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“…In the postnatal period, beta-cell replication is frequently seen within the first five years of life [29,51], but it is rarely seen thereafter in humans [14,38]. Based on the finding that endocrine and exocrine pancreas have a common origin during pancreas development, as described above, the presence of cellular plasticity in the adult pancreas has been suggested and reviewed elsewhere [52]. Cellular plasticity such as beta-cell neogenesis from duct cells or transdifferentiation from acinar cells or other endocrine cells (e.g., alpha-cells) may contribute to newly formed betacells, in addition to beta-cell replication.…”

Section: Ink4amentioning

confidence: 99%

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

Saisho¹

2016

Rev Diabet Stud

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■ AbstractThe pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better.

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Section: Ink4amentioning

confidence: 99%

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

Saisho¹

2016

Rev Diabet Stud

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“…Establishment of the pancreatic lineage is orchestrated by a network of TFs, including Pdx1, Ptf1a and Sox9 (Pan and Wright, 2011;Stanger and Hebrok, 2013). Chromatin states at lineagespecific regulatory regions in embryonic endoderm progenitors and in different stages of their descendants to pancreatic fate have been recently mapped (Avrahami and Kaestner, 2012;Wang et al, 2015;Xie et al, 2013;Xu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The histone methyltransferase Setd7 promotes pancreatic progenitor identity

2016

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Cell fate specification depends on transcriptional activation driven by lineage-specific transcription factors as well as changes in chromatin organization. To date, the interplay between transcription factors and chromatin modifiers during development is not well understood. We focus here on the initiation of the pancreatic program from multipotent endodermal progenitors. Transcription factors that play key roles in regulating pancreatic progenitor state have been identified, but the chromatin regulators that help to establish and maintain pancreatic fate are less well known. Using a comparative approach, we identify a crucial role for the histone methyltransferase Setd7 in establishing pancreatic cell identity. We show that Setd7 is expressed in the prospective pancreatic endoderm of Xenopus and mouse embryos prior to Pdx1 induction. Importantly, we demonstrate that setd7 is sufficient and required for pancreatic cell fate specification in Xenopus. Functional and biochemical approaches in Xenopus and mouse endoderm support that Setd7 modulates methylation marks at pancreatic regulatory regions, possibly through interaction with the transcription factor Foxa2. Together, these results demonstrate that Setd7 acts as a central component of the transcription complex initiating the pancreatic program.

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“…Several of the disease phenotypes are currently considered to involve the underlying state of adult stem cells, which are located throughout the body and are involved in the maintenance, regeneration and repair of the majority, or all, human tissues. The pancreas may represent an exception, where the somatic cells themselves replicate (4). As regards aging, although the effects are tissue-dependent, certain tissues exhibit a decline in stem cell numbers during the aging process, while other tissues may exhibit an increase.…”

Section: Introductionmentioning

confidence: 99%