naa a22 4500 510739490 CHVBK 20180411083023.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s12015-013-9435-6 doi (NATIONALLICENCE)springer-10.1007/s12015-013-9435-6 Role of BMP Signaling in Pancreatic Progenitor Differentiation from Human Embryonic Stem Cells [Elektronische Daten] [Lina Sui, Mieke Geens, Karen Sermon, Luc Bouwens, Josué Mfopou] Transplantation of pancreatic progenitors derived from human embryonic stem cells (hESCs) is a promising way to treat diabetes. Strategies to obtain the required cell mass would rely on the up scaling of current differentiation protocols, or the proliferation of committed progenitors. We aimed at finding conditions that maintain a proliferating pancreatic progenitor pool and we assessed the role of BMP4 signaling in this process. hESCs were differentiated into PDX1 positive pancreatic progenitor stage following our established protocol with few modifications, and then the progenitor cells were passaged in a defined proliferation medium (PM). During passage, the effect of BMP4 signaling on the differentiation and proliferation of pancreatic progenitors was examined by RT-PCR and immunofluorescence analysis. We found that PDX1 positive pancreatic progenitors proliferated and gained NKX6.1 expression in the PM, whereas they failed to express NKX6.1 if BMP signaling was inhibited with Noggin. In this latter condition, part of the progenitors rather generated pro-endocrine cells denoted by NGN3 and synaptophysin expression. On the contrary, addition of BMP4 to the PM promoted the early derivation of PDX1 and NKX6.1 coexpressing pancreatic progenitors. Our findings are in line with mouse pancreas development, and indicate that BMP4 signaling is required for the derivation and maintenance of hESC-derived PDX1+NKX6.1+ pancreatic progenitors. These results are instructive for guiding the development of an efficient pancreas differentiation protocol in view of diabetes cell replacement therapy. Springer Science+Business Media New York, 2013 hESCs nationallicence Pancreatic progenitors nationallicence Proliferation nationallicence BMP4 nationallicence DE : Definitive endoderm nationallicence PPP : PDX1 positive pancreatic progenitor nationallicence PNP : PDX1 or NKX6.1 positive pancreatic progenitor nationallicence PNCP : PDX1 and NKX6.1 coexpressing pancreatic progenitor nationallicence PN : Passage number nationallicence SB : SB431542 nationallicence NG : Noggin nationallicence PM : Proliferation medium nationallicence Sui Lina Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut Geens Mieke Department of Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium aut Sermon Karen Department of Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium aut Bouwens Luc Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut Mfopou Josué Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/5(2013-10-01), 569-577 1550-8943 9:5<569 2013 9 12015 https://doi.org/10.1007/s12015-013-9435-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12015-013-9435-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sui Lina Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 700 1- Geens Mieke Department of Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium aut NATIONALLICENCE 700 1- Sermon Karen Department of Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium aut NATIONALLICENCE 700 1- Bouwens Luc Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 700 1- Mfopou Josué Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 773 0- Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/5(2013-10-01), 569-577 1550-8943 9:5<569 2013 9 12015 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer