Generation of pancreatic β cells from CD177+ anterior definitive endoderm
Open accessAbstract
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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Significant progress has been made at improving the function of SC-islets when compared to the original protocols.
“To this end, significant progress has been made at improving the function of SC-islets when compared to the original protocols,39,40,44,48,49”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [49]
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References 53 · Cited by 115
- Authors
- Mahaddalkar, P. U., Scheibner, K., Pfluger, S., Ansarullah, Sterr, M., Beckenbauer, J., Irmler, M., Beckers, J., Knöbel, S., & Lickert, H.
- Affiliations
- Helmholtz Munich (DE)
- Miltenyi Biotec (Germany) (DE)
- TUM Klinikum (DE)
- Corresponding author
- Lickert, Heiko
- Venue
- Nature Biotechnology
- Published
- 2020-04-27
- Volume
- 38
- Issue
- 9
- Pages
- 1061-1072
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W3018193307
- Cited by
- 115
- References
- 53
- Citations by year
- 2026: 20 · 2025: 9 · 2024: 26 · 2023: 16 · 2022: 18 · 2021: 21 · 2020: 5
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- pancreatic beta cells, CD177, human pluripotent stem cells, pancreatic progenitors, Wnt signaling, Nodal, BMP antagonists, liver differentiation
- MeSH terms
- Adolescent, Adult, Cell Differentiation, Cell Line, Endoderm, Female, Humans, Isoantigens, Liver, Male, Middle Aged, Pancreas, Receptors, Cell Surface, Biomarkers, Cytokines, Cell Lineage, Receptors, CXCR4, Pluripotent Stem Cells, Insulin-Secreting Cells, Young Adult, GPI-Linked Proteins, Wnt Signaling Pathway, Inducible T-Cell Co-Stimulator Ligand
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