2017
DOI: 10.1074/jbc.m117.812537
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Chemical reprogramming of mouse embryonic and adult fibroblast into endoderm lineage

Abstract: We report here an approach to redirecting somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts to epithelial-like cells with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting epithelial-like cells that can be further reprogrammed to endodermal progenitor cells. Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocy… Show more

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Cited by 20 publications
(20 citation statements)
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“…Mean ± SEM, t test, n = 3 modulator valproic acid (VPA, an HDAC inhibitor), signalling pathway regulators (CHIR99021, an inhibitor of GSK3β, and RepSOX, a TGFβR-1/ALK5 inhibitor), and enzyme activity regulators (Parnate, a non-selective monoamine oxidase inhibitor; forskolin, a potent adenylate cyclase activator; EPZ004777, a selective DOT1L inhibitor; and AM580, a selective RARα agonist). At present, in addition to ciPSCs [6][7][8][9], neural stem cells [34], induced multipotent mesenchymal stem cell-like cells [35], and endoderm-like cells [36] have been successfully obtained using chemicals alone. Additionally, cells originating from different germ layers subjected to chemical reprogramming undergo the same ciXEN intermediate state [7,10,37].…”
Section: Discussionmentioning
confidence: 99%
“…Mean ± SEM, t test, n = 3 modulator valproic acid (VPA, an HDAC inhibitor), signalling pathway regulators (CHIR99021, an inhibitor of GSK3β, and RepSOX, a TGFβR-1/ALK5 inhibitor), and enzyme activity regulators (Parnate, a non-selective monoamine oxidase inhibitor; forskolin, a potent adenylate cyclase activator; EPZ004777, a selective DOT1L inhibitor; and AM580, a selective RARα agonist). At present, in addition to ciPSCs [6][7][8][9], neural stem cells [34], induced multipotent mesenchymal stem cell-like cells [35], and endoderm-like cells [36] have been successfully obtained using chemicals alone. Additionally, cells originating from different germ layers subjected to chemical reprogramming undergo the same ciXEN intermediate state [7,10,37].…”
Section: Discussionmentioning
confidence: 99%
“…Finally, the authors confirmed the generality of their strategy by using the same mixture to convert adult fibroblast cells from mice into ciEPCs and ciHeps with the expected features and functions. The work from Li et al (10) provides an important complement to the study from Cao et al (9) in that they focus on a different intermediate, the chemically induced epithelial XENlike state, but similarly confirm that this state is critical for robust generation of functional neurons or hepatocyte-like cells from mouse fibroblasts. These authors showed that XENlike cells could also be captured in culture and form stable cell lines for long-term expansion in vitro (Ͼ20 passages).…”
mentioning
confidence: 90%
“…With a refined protocol in hand, they demonstrated efficient reprogramming of mouse embryonic fibroblasts into endodermal progenitor cells (ciEPCs), which could be captured in culture as stable cell lines that self-renew in vitro for Ͼ30 passages without changing endodermal features. Cao et al (9) further showed that ciEPCs could be efficiently converted into albumin-producing hepatocytes (ciHeps) that could rescue mice from liver failure. Finally, the authors confirmed the generality of their strategy by using the same mixture to convert adult fibroblast cells from mice into ciEPCs and ciHeps with the expected features and functions.…”
mentioning
confidence: 99%
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“…The objective of this study was to directly reprogram mouse embryonic fibroblasts (MEFs) into chondrocytes through cationic polysaccharide-gene nanoparticles transfection. MEFs have been extensively used in cell lines differentiation in tissue engineering as seed cells [16]. Increasing evidence indicates that the transcription factor Sox9 (a member of the Sox (Sry-type HMGbox) proteins family) plays an essential role in chondrogenesis [17,18].…”
Section: Introductionmentioning
confidence: 99%