Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells

Nostro, M. Cristina; Sarangi, Farida; Ogawa, Shinichiro; Holtzinger, Audrey; Corneo, Barbara; Li, Xueling; Micallef, Suzanne Jeanine; Park, In‐Hyun; Basford, Christina; Wheeler, Michael B.; Daley, George Q.; Elefanty, Andrew G.; Stanley, Edouard G.; Keller, Gordon

doi:10.1242/jcs.087957

Cited by 55 publications

(123 citation statements)

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“…Scale bars (a-e) 50 μm, (f) 15 μm lower in the INS:GFP + fraction than in human islets (ESM Fig. 7), confirming previous reports [11].…”

Section: Ins:gfp + Cells Compared With Human Isletssupporting

confidence: 89%

“…The 'Nostro protocol' [11] consistently generated insulin + cells in vitro from the INS GFP/w reporter line and a HES2 line. The use of hESC-derived INS:GFP + cells enabled us to correlate the results of gene expression with electrophysiological and ultrastructural studies of purified insulin + cells.…”

Section: Discussionmentioning

confidence: 99%

“…INS GFP/w and untargeted hESC (HES2) cell lines (ES Cell International, Singapore) approved by the Stem Cell Oversight Committee were differentiated for 22 days using the 'Nostro protocol' [11] (Fig. 1a); HES2 cells differentiated for 22 days are referred to as day 22 differentiated HES2 (d22-HES2).…”

Section: Hesc Culturementioning

confidence: 99%

“…1a); HES2 cells differentiated for 22 days are referred to as day 22 differentiated HES2 (d22-HES2). Following differentiation, INS GFP/w were FACS-sorted into GFP-producing (INS:GFP + ) and GFPnegative (INS:GFP − ) fractions [11].…”

Section: Hesc Culturementioning

confidence: 99%

“…We recently developed and characterised a 22-day differentiation protocol that more efficiently generates insulin-producing cells from hESCs [11] (Fig. 1a).…”

Section: Introductionmentioning

confidence: 99%

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The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells

et al. 2011

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INS:GFP(+) cells can be purified from differentiated hESCs, providing a superior source of insulin-producing cells. Genomic analyses revealed that INS:GFP(+) cells collectively resemble immature endocrine cells. However, insulin(+) cells were heterogeneous, a fact that translated into important functional differences within this population. The information gained from this study may now be used to generate new iterations of functioning beta cells that can be purified for transplant.

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“…Scale bars (a-e) 50 μm, (f) 15 μm lower in the INS:GFP + fraction than in human islets (ESM Fig. 7), confirming previous reports [11].…”

Section: Ins:gfp + Cells Compared With Human Isletssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Hesc Culturementioning

confidence: 99%

Section: Hesc Culturementioning

confidence: 99%

“…We recently developed and characterised a 22-day differentiation protocol that more efficiently generates insulin-producing cells from hESCs [11] (Fig. 1a).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells

et al. 2011

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Transplantation Models to Characterize the Mechanisms of Stem Cell–Induced Islet Regeneration

Bell

Seneviratne

Nasri

et al. 2013

CP Stem Cell Biology

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This unit describes our current knowledge regarding the isolation human bone marrow–derived progenitor cells for the paracrine stimulation of islet regeneration after transplantation into immunodeficient mouse models of diabetes. By using high aldehyde dehydrogenase (ALDHhi) activity, a conserved function in multiple stem cell lineages, a mixed population of hematopoietic, endothelial, and mesenchymal progenitor cells can be efficiently purified using flow cytometry. We describe in vitro approaches to characterize and expand these distinct cell types. Importantly, these cell types can be transplanted into immunodeficient mice rendered beta‐cell deficient by streptozotocin (STZ) treatment, in order monitor functional recovery from hyperglycemia and to characterize endogenous islet regeneration via paracrine mechanisms. Herein, we provide detailed protocols for: (1) isolation and characterization of ALDHhi cells for the establishment of hematopoietic and multipotent‐stromal progenitor lineages; (2) intravenous and intrapancreatic transplantation of human stem cell subtypes for the quantification of glycemic recovery in STZ‐treated immunodeficient mice; and (3) immunohistochemical characterization of islet recovery via the stimulation of islet neogenic, beta‐cell proliferative, and islet revascularization programs. Collectively, these systems can be used to support the pre‐clinical development of human progenitor cell–based therapies to treat diabetes via islet regeneration. Curr. Protoc. Stem Cell Biol. 26:2B.4.1‐2B.4.35. © 2013 by John Wiley & Sons, Inc.

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Derivation of Endodermal Progenitors From Pluripotent Stem Cells

Ikonomou

Kotton

2014

Journal Cellular Physiology

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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.

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Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells

Cited by 55 publications

References 1 publication

The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells

The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells

Transplantation Models to Characterize the Mechanisms of Stem Cell–Induced Islet Regeneration

Derivation of Endodermal Progenitors From Pluripotent Stem Cells

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