Spatiotemporal patterns of multipotentiality in <i>Ptf1a</i>-expressing cells during pancreas organogenesis and injury-induced facultative restoration

Pan, Fong Cheng; Bankaitis, Eric D.; Boyer, Daniel F.; Xu, Xiaobo; Casteele, Mark Van de; Magnuson, Mark A.; Heimberg, Harry; Wright, Christopher V.E.

doi:10.1242/dev.090159

Cited by 267 publications

(302 citation statements)

References 37 publications

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“…β cells express pancreatic and duodenal homeobox 1 (Pdx1) and NK6 homeobox 1 (Nkx6.1) (12). Consistently, the Sox9/EGFP + Ins + cells in the GE-treated recipients also expressed Pdx1 and Nkx6.1 (Fig.…”

Section: Resultssupporting

confidence: 55%

“…It has been proposed that β-cell neogenesis in adult mice can derive from pancreatic ductal cells (5,6), cells in the islet (7,8), transdifferentiation from glucagon-producing α cells (9,10), or from acinar cells (11)(12)(13). Although it has been consistently reported that pancreatic ductal epithelial cells give rise to insulin-producing β cells during embryonic development (14)(15)(16)(17), whether the pancreatic ductal progenitors can give rise to insulin-producing β cells in neonates and adult mice remains controversial.…”

mentioning

confidence: 99%

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Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes

Zhang

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9 + (Sox9 + ) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9 + ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin-or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9 + ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9 + ductal cell differentiation into β cells in adult mice.

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Section: Resultssupporting

confidence: 55%

mentioning

confidence: 99%

Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes

Zhang

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…111,112 Recently, a study described the expression of Ptf1a C MPCs during pancreatic organogenesis. 113 Limited Ptf1a C cells were identified during the secondary transition and later Ptf1a C cells were confined to acinar cells. 113 113 Upon streptozotocin (Stz) administration, acinar trans-differentiation to endocrine/b-cells was enhanced.…”

Section: Sex Determining Region Y Box 17 (Sox 17)mentioning

confidence: 99%

“…113 Limited Ptf1a C cells were identified during the secondary transition and later Ptf1a C cells were confined to acinar cells. 113 113 Upon streptozotocin (Stz) administration, acinar trans-differentiation to endocrine/b-cells was enhanced. 113 Sex determining region Y Box 9 (Sox 9)…”

Section: Sex Determining Region Y Box 17 (Sox 17)mentioning

confidence: 99%

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Transcription factor regulation of pancreatic organogenesis, differentiation and maturation

Dassaye

Naidoo

Cerf

2015

Islets

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Lineage tracing studies have revealed that transcription factors play a cardinal role in pancreatic development, differentiation and function. Three transitions define pancreatic organogenesis, differentiation and maturation. In the primary transition, when pancreatic organogenesis is initiated, there is active proliferation of pancreatic progenitor cells. During the secondary transition, defined by differentiation, there is growth, branching, differentiation and pancreatic cell lineage allocation. The tertiary transition is characterized by differentiated pancreatic cells that undergo further remodeling, including apoptosis, replication and neogenesis thereby establishing a mature organ. Transcription factors function at multiple levels and may regulate one another and auto-regulate. The interaction between extrinsic signals from non-pancreatic tissues and intrinsic transcription factors form a complex gene regulatory network ultimately culminating in the different cell lineages and tissue types in the developing pancreas. Mutations in these transcription factors clinically manifest as subtypes of diabetes mellitus. Current treatment for diabetes is not curative and thus, developmental biologists and stem cell researchers are utilizing knowledge of normal pancreatic development to explore novel therapeutic alternatives. This review summarizes current knowledge of transcription factors involved in pancreatic development and b-cell differentiation in rodents.

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Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice

Cavelti-Weder

Zumsteg

et al. 2017

CP Stem Cell Biology

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To generate new beta-cells after birth is a key focus of regenerative medicine that could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: 1) the development of beta-cells from putative precursor cells of the adult pancreas termed neogenesis, 2) replication of existing beta-cells, 3) differentiation from embryonic or induced pluripotent stem cells, and 4) reprogramming of non-beta to beta-cells. Studies from our laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA. This protocol outlines the generation of a polycistronic construct containing the three transcription factors, the expansion and purification of the polycistronic virus and in vivo transduction for acinar to beta-cell reprogramming in adult mice. The ultimate goal is to generate beta-like cells that resemble endogenous beta-cells in phenotype and function as closely as possible for potential translational applications.

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Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration

Cited by 267 publications

References 37 publications

Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes

Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes

Transcription factor regulation of pancreatic organogenesis, differentiation and maturation

Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice

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Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration

Cited by 267 publications

References 37 publications

Growth factors and medium hyperglycemia induce Sox9+ductal cell differentiation into β cells in mice with reversal of diabetes

Growth factors and medium hyperglycemia induce Sox9+ductal cell differentiation into β cells in mice with reversal of diabetes

Transcription factor regulation of pancreatic organogenesis, differentiation and maturation

Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice

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Product

Resources

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Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes

Growth factors and medium hyperglycemia induce Sox9⁺ductal cell differentiation into β cells in mice with reversal of diabetes