Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2

Cerdá-Esteban, Nuria; Naumann, Heike; Ruzittu, Silvia; Mah, Nancy; Pongrac, I; Cozzitorto, Corinna; Hommel, Angela; Andrade‐Navarro, Miguel A.; Bonifacio, Ezio; Spagnoli, Francesca

doi:10.1038/ncomms14127

Cited by 44 publications

(37 citation statements)

References 69 publications

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“…These studies together suggest that gastrointestinal epithelial cells are a potential source of functional insulin-expressing cells by reprogramming. Other examples of reprogramming mouse cells include cytokine-mediated conversion of acinar cells to insulin-expressing cells, conversion of duct cells to insulin-expressing cells byFBW7 deletion, and conversion of hepatocytes to insulin-producing cells by TGIF2 114–116 .…”

Section: Strategies To Produce New Endocrine Islet Cellsmentioning

confidence: 99%

Pancreas regeneration

Zhou¹,

Melton²

2018

Nature

306

200

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The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals. Together these approaches form a rich pipeline of therapeutic development for pancreatic regeneration.

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Section: Strategies To Produce New Endocrine Islet Cellsmentioning

confidence: 99%

Pancreas regeneration

Zhou¹,

Melton²

2018

Nature

306

200

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“…3). Several studies have demonstrated that adult or fetal liver cells and biliary epithelial cells are capable of reprogramming into IPCs by inducing the expression of endocrine pancreaticspecific transcription factors [95][96][97][98]. The in vivo data showed that these hepatic cell-derived IPCs could ameliorate hyperglycemia upon implantation into diabetic mice.…”

Section: Differentiation Of Liver Cellsmentioning

confidence: 99%

Current progress in stem cell therapy for type 1 diabetes mellitus

2020

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Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies. Attempts have been directed to accommodate the increasing population of patients with T1DM. Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients. In this review, we discuss the current research advances in strategies to obtain insulin-producing cells (IPCs) from different precursor cells and in stem cell-based therapies for diabetes.

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“…As demonstrated in Figure S3C, all pancreatic-related makers remained at a very low level. A number of genes that have been detected in both pancreatic progenitors and liver, such as MafA, Hhex, and Prox1 (Cerda-Esteban et al., 2017, Huang et al., 2014), were found to increase in a time-dependent way during iHep induction; and, at day 18, the expression of those three genes in the iHep induction systems were similar to hepatocytes. Moreover, the intestinal genes such as Secretin and Chromogranin A were not detected (Figure S3C).…”

Section: Resultsmentioning

confidence: 99%

Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor

et al. 2017

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SummaryLiver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah−/−) mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps.

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Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2

Cited by 44 publications

References 69 publications

Pancreas regeneration

Pancreas regeneration

Current progress in stem cell therapy for type 1 diabetes mellitus

Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor

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