Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules

Kearns, Nicola A.; Genga, Ryan M.; Ziller, Michael J.; Kapinas, Kristina; Peters, Heiko; Brehm, Michael A.; Meissner, Alexander; Maehr, René

doi:10.1016/j.scr.2013.06.007

Cited by 36 publications

(26 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Green et al showed that dual inhibition of BMP‐ and Nodal/TGF‐β specified an AFE population. These results were recently reproduced by other reports although Kearns et al found that TGF‐β and BMP‐inhibition were not necessarily required. In contrast to that Hannan et al reported that activin A by Nodal/TGF‐β activation can direct endoderm into a SOX2‐positive AFE cell population that could be expanded into a foregut stem cell line capable of pancreatic and hepatic lineage commitment.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Anterior–Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

et al. 2016

View full text Add to dashboard Cite

As known from model organisms, such as frog, fish, mouse, and chicken, the anterior-posterior patterning of the definitive endoderm (DE) into distinct domains is controlled by a variety of signaling interactions between the DE and its surrounding mesoderm. This includes Wnt/FGFs and BMPs in the posterior half and all-trans-retinoic acid, TGF-β-ligands, Wnt-, and BMP-inhibitors in the anterior half of the DE sheet. However, it is currently unclear how these embryonic tissue interactions can be translated into a defined differentiation protocol for human embryonic stem cells. Activin A has been proposed to direct DE into a SOX2-positive foregut-like cell type. Due to the pleiotropic nature of SOX2 in pluripotency and developing cells of the foregut, we purified DE-cells by magnetic cell sorting and tested the effects of anteriorizing and posteriorizing factors on pure endoderm. We show in contrast to previous studies that the generation of the foregut marked by SOX2/FOXA2 double-positive cells does not depend on activin A/TGF-β-signaling but is mediated by the inhibition of Wnt- and BMP-signaling. Retinoic acid can posteriorize and at the same time dorsalize the foregut toward a PDX1-positive pancreatic duodenal cell type whereas active Wnt/beta-catenin signaling synergistically with FGF-2, BMP-4, and RA induces the formation of CDX2-positive posterior endoderm. Thus, these results provide new insights into the mechanisms behind cell specification of human DE derived from pluripotent stem cells. Stem Cells 2016;34:2635-2647.

show abstract

Section: Discussionsupporting

confidence: 83%

“…Several groups analyzed the mechanisms underlying the endoderm patterning into the foregut [10,11,[13][14][15][16] and hindgut [12,13,16]. Ameri et al [11] described that FGF-4 together with RA patterns the endoderm into PFE.…”

Section: Discussionmentioning

confidence: 99%

Anterior–Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

et al. 2016

View full text Add to dashboard Cite

show abstract

“…They are also progenitor r celsl for Type I Alveolar cells. Anterior Foregut Endoderm (AFE) : AFE gives rise to cell types such as esophagus, salivary glands, lung, thymus, parathyroid and thyroid glands. This tissue became the target for differentiation from iPSCs, and its heterogeneity could be an obstacle for trying to create lung‐specific cells AQP : aquaporin.…”

Section: Glossarymentioning

confidence: 99%

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Pollard¹,

Pollard

2018

Pediatric Pulmonology

View full text Add to dashboard Cite

Induced pluripotent stem cells (iPSCs) are a recently developed technology in which fully differentiated cells such as fibroblasts from individual CF patients can be repaired with [wildtype] CFTR, and reprogrammed to differentiate into fully differentiated cells characteristic of the proximal and distal airways. Here, we review properties of different epithelial cells in the airway, and the in vitro genetic roadmap which iPSCs follow as they are step-wise differentiated into either basal stem cells, for the proximal airway, or into Type II Alveolar cells for the distal airways. The central theme is that iPSC-derived basal stem cells, are penultimately dependent on NOTCH signaling for differentiation into club cells, goblet cells, ciliated cells, and neuroendocrine cells. Furthermore, given the proper matrix, these cellular progenies are also able to self-assemble into a fully functional pseudostratified squamous proximal airway epithelium. By contrast, club cells are reserve stem cells which are able to either differentiate into goblet or ciliated cells, but also to de-differentiate into basal stem cells. Variant club cells, located at the transition between airway and alveoli, may also be responsible for differentiation into Type II Alveolar cells, which then differentiate into Type I Alveolar cells for gas exchange in the distal airway. Using gene editing, the mutant CFTR gene in iPSCs from CF patients can be repaired, and fully functional epithelial cells can thus be generated through directed differentiation. However, there is a limitation in that the lung has other CFTR-dependent cells besides epithelial cells. Another limitation is that there are CFTR-dependent cells in other organs which would continue to contribute to CF disease. Furthermore, there are also bystander or modifier genes which affect disease outcome, not only in the lung, but specifically in other CF-affected organs. Finally, we discuss future personalized applications of the iPSC technology, many of which have already survived the "proof-of-principle" test. These include (i) patient-derived iPSCs used as a "lung-on-a-chip" tool for personalized drug discovery; (ii) replacement of mutant lung cells by wildtype lung cells in the living lung; and (iii) development of bio-artificial lungs. It is hoped that this review will give the reader a roadmap through the most complicated of the obstacles, and foster a guardedly optimistic view of how some of the remaining obstacles might one day be overcome.

show abstract

“…Three recent studies have reported efficient derivation of AFE progenitors from PSCs in vitro (Green et al, 2011;Brafman et al, 2013a;Kearns et al, 2013). Snoeck and colleagues demonstrated that inhibition of BMP4 and TGF-b signaling at the DE stage of hES or iPS cell directed differentiation leads to AFE derivation as witnessed by the reduced expression of hepatic and intestinal markers and the up-regulation of anterior markers such as SOX2, TBX1, NKX2-5 and PAX9 (Green et al, 2011).…”

Section: Anterior Foregut Progenitorsmentioning

confidence: 99%

Derivation of Endodermal Progenitors From Pluripotent Stem Cells

Ikonomou

Kotton

2014

Journal Cellular Physiology

View full text Add to dashboard Cite

Stem and progenitor cells play important roles in organogenesis during development and in tissue homeostasis and response to injury postnatally. As the regenerative capacity of many human tissues is limited, cell replacement therapies hold great promise for human disease management. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are prime candidates for the derivation of unlimited quantities of clinically relevant cell types through development of directed differentiation protocols, i.e. the recapitulation of developmental milestones in in vitro cell culture. Tissue-specific progenitors, including progenitors of endodermal origin, are important intermediates in such protocols since they give rise to all mature parenchymal cells. In this review, we focus on the in vivo biology of embryonic endodermal progenitors in terms of key transcription factors and signaling pathways. We critically review the emerging literature aiming to apply this basic knowledge to achieve the efficient and reproducible in vitro derivation of endodermal progenitors such as pancreas, liver and lung precursor cells.

show abstract

Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules

Cited by 36 publications

References 14 publications

Anterior–Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

Anterior–Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Derivation of Endodermal Progenitors From Pluripotent Stem Cells

Contact Info

Product

Resources

About