Transcriptional dynamics of induced pluripotent stem cell differentiation into β cells reveals full endodermal commitment and homology with human islets
| Autor: | Marta Tiffany Lombardo, Fabio Manenti, Francesca Giannese, Gaia Poggi, Lorenzo Piemonti, Rita Nano, Silvia Pellegrini, Raniero Chimienti, G. Scotti, Alessandro Cospito, Valeria Sordi, Dejan Lazarevic |
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| Přispěvatelé: | Pellegrini, Silvia, Chimienti, Raniero, Scotti, Giulia Maria, Giannese, Francesca, Lazarevic, Dejan, Manenti, Fabio, Poggi, Gaia, Lombardo, Marta Tiffany, Cospito, Alessandro, Nano, Rita, Piemonti, Lorenzo, Sordi, Valeria |
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Cancer Research induced pluripotent stem cells Immunology Induced Pluripotent Stem Cells Enteroendocrine cell Cell fate determination Biology Homology (biology) single-cell RNA sequencing Transcriptome 03 medical and health sciences Islets of Langerhans 0302 clinical medicine medicine Immunology and Allergy Humans Induced pluripotent stem cell Genetics (clinical) Transplantation β-cell differentiation Endoderm RNA Cell Differentiation Cell Biology endocrine cells In vitro Cell biology 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis pseudotime |
| Zdroj: | Cytotherapy |
| ISSN: | 1465-3249 |
| DOI: | 10.1016/j.jcyt.2020.10.004 |
| Popis: | Background aims Induced pluripotent stem cells (iPSCs) have the capacity to generate β cells in vitro, but the differentiation is incomplete and generates a variable percentage of off-target cells. Single-cell RNA sequencing offers the possibility of characterizing the transcriptional dynamics throughout differentiation and determining the identity of the final differentiation product. Methods Single-cell transcriptomics data were obtained from four stages across differentiation of iPSCs into β cells and from human donor islets. Results Clustering analysis revealed that iPSCs undertake a full endoderm commitment, and the obtained endocrine pancreatic cells have high homology with mature islets. The iPSC-derived β cells were devoid of pluripotent residual cells, and the differentiation was pancreas-specific, as it did not generate ectodermal or mesodermal cells. Pseudotime trajectory identified a dichotomic endocrine/non-endocrine cell fate and distinct subgroups in the endocrine branch. Conclusions Future efforts to produce β cells from iPSCs must aim not only to improve the resulting endocrine cell but also to avoid differentiation into non-pancreatic endoderm cells. |
| Databáze: | OpenAIRE |
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