Wnt signaling: implications in endoderm development and pancreas organogenesis

Scheibner, Katharina; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko

doi:10.1016/j.ceb.2019.07.002

Cited by 34 publications

(16 citation statements)

References 71 publications

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“…Wnt signaling pathway is known to be fundamental for the endocrinogenesis process during the embryonic development [117,118,119]. A recent study has also engaged the use of a Wnt/PCP effector protein, Fltp, to demonstrate the association between non-canonical Wnt signaling and the β-cell maturation phenotype [86].…”

Section: Postnatal Development: Road To Maturitymentioning

confidence: 99%

β-Cell Maturation and Identity in Health and Disease

Salinno

Cota

Bastidas-Ponce

et al. 2019

IJMS

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The exponential increase of patients with diabetes mellitus urges for novel therapeutic strategies to reduce the socioeconomic burden of this disease. The loss or dysfunction of insulin-producing β-cells, in patients with type 1 and type 2 diabetes respectively, put these cells at the center of the disease initiation and progression. Therefore, major efforts have been taken to restore the β-cell mass by cell-replacement or regeneration approaches. Implementing novel therapies requires deciphering the developmental mechanisms that generate β-cells and determine the acquisition of their physiological phenotype. In this review, we summarize the current understanding of the mechanisms that coordinate the postnatal maturation of β-cells and define their functional identity. Furthermore, we discuss different routes by which β-cells lose their features and functionality in type 1 and 2 diabetic conditions. We then focus on potential mechanisms to restore the functionality of those β-cell populations that have lost their functional phenotype. Finally, we discuss the recent progress and remaining challenges facing the generation of functional mature β-cells from stem cells for cell-replacement therapy for diabetes treatment.

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Section: Postnatal Development: Road To Maturitymentioning

confidence: 99%

β-Cell Maturation and Identity in Health and Disease

Salinno

Cota

Bastidas-Ponce

et al. 2019

IJMS

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“…These data suggest that Bdh2 is involved in the proper control of germ layer specific transcripts for cell fate decision. Wnt and Nodal signaling play a critical role in endoderm formation (Scheibner et al, 2019), our study show that Wnt signaling was the top pathway enriched in the Bdh2deficient ASCs; it would be interesting to investigate how Bdh2 regulates Wnt signaling, which in turn controls cell fate decision during germ layer differentiation.…”

Section: Discussionmentioning

confidence: 82%

Bdh2 Deficiency Promotes Endoderm-Biased Early Differentiation of Mouse Embryonic Stem Cells

Liu

Cao

et al. 2021

Front. Cell Dev. Biol.

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3-hydroxybutyrate dehydrogenase-2 (Bdh2), a short-chain dehydrogenase, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore, playing a key role in iron homeostasis, energy metabolism and apoptosis. However, the function of Bdh2 in embryonic stem cells (ESCs) remains unknown. To gain insights into the role of Bdh2 on pluripotency and cell fate decisions of mouse ESCs, we generated Bdh2 homozygous knockout lines for both mouse advanced embryonic stem cell (ASC) and ESC using CRISPR/Cas9 genome editing technology. Bdh2 deficiency in both ASCs and ESCs had no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of Bdh2 for self-renewal and pluripotency of ESCs. Interestingly, cells with Bdh2 deficiency exhibited potency of endoderm differentiation in vitro; with upregulated endoderm associated genes revealed by RNA-seq and RT-qPCR. We further demonstrate that Bdh2 loss inhibited expression of multiple methyltransferases (DNMTs) at both RNA and protein level, suggesting that Bdh2 may be essentially required to maintain DNA methylation in ASCs and ESCs. Overall, this study provides valuable data and resources for understanding how Bdh2 regulate earliest cell fate decision and DNA methylation in ASCs/ESCs.

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“…Because Wnt signaling is essential for endoderm differentiation, not only activin A but also Wnt−3α are used to induce endoderm from human iPSCs [41]. Moreover, FGF signaling is important for endoderm differentiation because it regulates epithelial-tomesenchymal transition (EMT) [42].…”

Section: Discussionmentioning

confidence: 99%

An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes

Qiu

Imakura

et al. 2021

Cells

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The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption and metabolism. The development of human iPSC-derived enterocytes (HiEnts) and hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency of these cells remains to be elucidated. Here, we aimed to develop an efficient differentiation method to induce endoderm formation from human iPSCs. Cells treated with activin A for 168 h expressed higher levels of endodermal genes than those treated for 72 h. Using activin A (days 0–7), CHIR99021 and PI−103 (days 0–2), and FGF2 (days 3–7), the hiPSC-derived endoderm (HiEnd) showed 97.97% CD−117 and CD−184 double-positive cells. Moreover, HiEnts derived from the human iPSC line Windy had similar or higher expression of small intestine-specific genes than adult human small intestine. Activities of the drug transporter P-glycoprotein and drug-metabolizing enzyme cytochrome P450 (CYP) 3A4/5 were confirmed. Additionally, Windy-derived HiHeps expressed higher levels of hepatocyte- and pharmacokinetics-related genes and proteins and showed higher CYP3A4/5 activity than those derived through the conventional differentiation method. Thus, using this novel method, the differentiated HiEnts and HiHeps with pharmacokinetic functions could be used for drug development.

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Wnt signaling: implications in endoderm development and pancreas organogenesis

Cited by 34 publications

References 71 publications

β-Cell Maturation and Identity in Health and Disease

β-Cell Maturation and Identity in Health and Disease

Bdh2 Deficiency Promotes Endoderm-Biased Early Differentiation of Mouse Embryonic Stem Cells

An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes

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