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Tytuł pozycji:

Generation of pancreatic β cells from CD177 + anterior definitive endoderm.

Tytuł:
Generation of pancreatic β cells from CD177 anterior definitive endoderm.
Autorzy:
Mahaddalkar PU; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.; Institute of Stem Cell Research, Helmholtz Zentrum München, Neuherberg, Germany.
Scheibner K; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.
Pfluger S; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.
Ansarullah; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.
Sterr M; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.; Institute of Stem Cell Research, Helmholtz Zentrum München, Neuherberg, Germany.
Beckenbauer J; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.
Irmler M; Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Beckers J; Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.; Chair of Experimental Genetics, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Knöbel S; Miltenyi Biotec, Bergisch Gladbach, Germany.
Lickert H; Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany. .; Institute of Stem Cell Research, Helmholtz Zentrum München, Neuherberg, Germany. .; German Center for Diabetes Research (DZD), Neuherberg, Germany. .; β-Cell Biology, Technische Universität München, School of Medicine, Klinikum Rechts der Isar, Munich, Germany. .
Źródło:
Nature biotechnology [Nat Biotechnol] 2020 Sep; Vol. 38 (9), pp. 1061-1072. Date of Electronic Publication: 2020 Apr 27.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: New York Ny : Nature America Publishing
Original Publication: New York, NY : Nature Pub. Co., [1996-
MeSH Terms:
Endoderm/*cytology
Endoderm/*metabolism
Insulin-Secreting Cells/*cytology
Isoantigens/*metabolism
Receptors, Cell Surface/*metabolism
Adolescent ; Adult ; Biomarkers/metabolism ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cytokines/metabolism ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Inducible T-Cell Co-Stimulator Ligand/metabolism ; Insulin-Secreting Cells/metabolism ; Liver/cytology ; Liver/metabolism ; Male ; Middle Aged ; Pancreas/cytology ; Pancreas/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Receptors, CXCR4/metabolism ; Wnt Signaling Pathway/physiology ; Young Adult
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Substance Nomenclature:
0 (Biomarkers)
0 (CD177 protein, human)
0 (CER1 protein, human)
0 (CXCR4 protein, human)
0 (Cytokines)
0 (GPI-Linked Proteins)
0 (ICOSLG protein, human)
0 (Inducible T-Cell Co-Stimulator Ligand)
0 (Isoantigens)
0 (Receptors, CXCR4)
0 (Receptors, Cell Surface)
Entry Date(s):
Date Created: 20200429 Date Completed: 20201109 Latest Revision: 20220422
Update Code:
20240105
DOI:
10.1038/s41587-020-0492-5
PMID:
32341565
Czasopismo naukowe
Methods for differentiating human pluripotent stem cells to pancreatic and liver lineages in vitro have been limited by the inability to identify and isolate distinct endodermal subpopulations specific to these two organs. Here we report that pancreatic and hepatic progenitors can be isolated using the surface markers CD177/NB1 glycoprotein and inducible T-cell costimulatory ligand CD275/ICOSL, respectively, from seemingly homogeneous definitive endoderm derived from human pluripotent stem cells. Anterior definitive endoderm (ADE) subpopulations identified by CD177 and CD275 show inverse activation of canonical and noncanonical WNT signaling. CD177 + ADE expresses and synthesizes the secreted WNT, NODAL and BMP antagonist CERBERUS1 and is specified toward the pancreatic fate. CD275 + ADE receives canonical Wnt signaling and is specified toward the liver fate. Isolated CD177 + ADE differentiates more homogeneously into pancreatic progenitors and into more functionally mature and glucose-responsive β-like cells in vitro compared with cells from unsorted differentiation cultures.

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