Cellular Plasticity within the Pancreas— Lessons Learned from Development

Puri, Sapna; Hebrok, Matthias

doi:10.1016/j.devcel.2010.02.005

Cited by 143 publications

(134 citation statements)

References 142 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…Second, the nonpancreatic cell populations that exist in the differentiation cultures complicate the studies of pancreatic differentiation and limit the practicality of a large-scale screen. In fetal pancreatic development, epithelium-mesenchyme, epithelium-endothelium, and endothelium-mesenchyme interactions occur simultaneously and synergistically determine pancreatic progenitor maintenance, endocrine-exocrine regionalization, islet cell differentiation, and maturation through supportive or inhibitory effects [20,21]. Signals derived from nonpancreatic lineages are varied, temporal-dependent, and critical for pancreatic lineage differentiation.…”

Section: Discussionmentioning

confidence: 99%

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

et al. 2011

View full text Add to dashboard Cite

Human ESCs provide a promising cell resource for the treatment of type I diabetes mellitus. Although PDX1-positive pancreatic progenitors can be efficiently generated from human ESCs by stepwise induction, further in vitro differentiation into functional, mature beta cells is not efficient or reproducible. Purification of pancreatic progenitor cells could facilitate the identification of signals that regulate beta cell differentiation and maturation. Here, we report the identification of a novel surface marker for PDX1-positive pancreatic progenitors based on an in vitro human ESC differentiation system. By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. CD24-positive cells coexpressed most of the key transcription factors of pancreatic progenitors, and the expression of important pancreatic genes was greatly enriched in CD24-positive cells compared with the CD24-negative cells. In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. Enrichment of pancreatic progenitors with this marker will facilitate the investigation of beta cell maturation during the human ESC differentiation.

show abstract

Section: Discussionmentioning

confidence: 99%

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The differentiation of these distinct endocrine cell types is coordinately controlled by multiple transcription factors and regulators (Fig. 2) [1,7,8]. Among these transcription factors, a key regulator of endocrine specification is Neurogenin 3 (Neurog3, also known as Atoh5), a member of the basic helixloop-helix (bHLH) transcription factor family.…”

Section: Brief Overview Of Endocrine Differentiationmentioning

confidence: 99%

Chronology of endocrine differentiation and beta-cell neogenesis [Review]

Miyatsuka

2016

Endocr J

View full text Add to dashboard Cite

Abstract. Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo. Key words: Endocrine progenitor, Beta cell neogenesis, Endocrine differentiation Understanding Endocrine Differentiation towards Developing a Cure for DiabetesDiabetes mellitus is a chronic metabolic disorder, which can lead to serious complications, such as blindness, kidney failure, amputation, cardiac problems, stroke, etc. A hallmark sign of diabetes is the sustained elevation of blood glucose levels, which results from absolute or relative deficiency of insulin-secreting beta cells within the pancreatic islets. There are several strategies proposed to maintain or expand beta-cell mass (Fig. 1), such as inducing cellular reprogramming into beta cells from somatic cells as well as embryonic stem cells, and stimulating the self-renewal of preexisting beta cells [1]. Because many pancreas-specific genes that play important roles in pancreas development are expressed during the process of cellular reprogramming towards a beta-cell phenotype, clarifying the molecular mechanisms of pancreas development and transcriptional networks should give us clues towards generating insulin-secreting beta cells, which can be used to cure diabetes. For example, it has been demonstrated that three transcription factors, namely, Pdx1, Neurog3, and Mafa, which play key roles in pancreas development and differentiation (Fig. 2), efficiently promoted the cellular reprogramming of nonbeta cells into insulin-producing cells [2−6]. Brief Overview of Endocrine DifferentiationThe mature pancreas is composed of exocrine (acinar and duct cells) and endocrine (α-, β-, δ-, ε-, and PP-cells) compartments, which express glucagon, insulin, somatostatin, ghrelin, and pancreatic polypeptide, respectively. The differentiation of these distinct endocrine cell types is coordinately controlled by multiple transcription factors and regulators (Fig. 2) [1,7,8]. Among these transcription factors, a key regulator of endocrine specification is Neurogenin 3 (Neurog3, also known as Atoh5), a member of the basic helixloop-helix (bHLH) transcription factor family. During pancreas d...

show abstract

“…The pancreas is a mixed exocrine and endocrine gland responsible for vital functions in our body, including the digestion and glucose metabolism. 6,7 During embryonic development, the pancreas originates from distinct embryonic outgrowths of the dorsal and ventral primitive gut endoderm at embryonic day (E) 9.5 in the mouse embryo. 7,8 Both outgrowths evaginate into the surrounding mesenchyme as solid epithelial buds, which subsequently undergo proliferation, differentiation and morphogenesis and, eventually, fuse together to form the definitive organ.…”

mentioning

confidence: 99%

“…6,7 During embryonic development, the pancreas originates from distinct embryonic outgrowths of the dorsal and ventral primitive gut endoderm at embryonic day (E) 9.5 in the mouse embryo. 7,8 Both outgrowths evaginate into the surrounding mesenchyme as solid epithelial buds, which subsequently undergo proliferation, differentiation and morphogenesis and, eventually, fuse together to form the definitive organ. 7,8 Recent evidence suggests that pancreatic organ size is constrained by the initial progenitor population.…”

mentioning

confidence: 99%

RhoGAP control of pancreas development

Zygmunt

Spagnoli²

2013

Small GTPases

View full text Add to dashboard Cite

R ecent evidences suggested that growth and differentiation of pancreatic cell lineages, including the insulin-producing β-cells, depend on proper tissue-architecture, epithelial remodeling and cell positioning within the branching pancreatic epithelium. We recently found that Rho GTPase and its regulator, Stard13 RhoGAP, coordinate morphogenesis with growth in the developing pancreas. Conditional mutation of Stard13 in the mouse pancreas hampers epithelial remodeling and distal tip domain formation, affecting proliferation and expansion of pancreatic progenitors. These defects eventually result in pancreatic hypoplasia at birth. Stard13 acts by regulating Rho signaling spatially and temporally during pancreas development. In line with this, pharmacological activation or inhibition of Rho mimics or rescues, respectively, the defects observed in Stard13-deficient embryos and pancreatic organ cultures. Furthermore, in the absence of Stard13 uninhibited Rho activity affects the actomyosin contractile network, disrupting its apical distribution and hampering coordinated cell-shape changes. These results unveil therefore the crucial role of actin cytoskeletal dynamics during the onset of pancreatic branching morphogenesis. Finally, our findings define a reciprocal interaction between the actin-MAL/SRF and the MAPK signaling to locally regulate progenitor cell proliferation in the pancreas.During embryogenesis developing organs acquire their final functional architectures at the same time as their residing cells

show abstract

Cellular Plasticity within the Pancreas— Lessons Learned from Development

Cited by 143 publications

References 142 publications

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

Chronology of endocrine differentiation and beta-cell neogenesis [Review]

RhoGAP control of pancreas development

Contact Info

Product

Resources

About