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Differentiated human stem cells resemble fetal, not adult, β cells
Open accessAbstract
Significance: Human pluripotent stem cells (hPSCs) can be produced from any person and have the potential to differentiate into any cell type in the body. This study focuses on the generation of insulin-expressing cells from hPSCs and compares their gene expression, as assayed by transcriptional gene products, to that of insulin-expressing β cells from human fetal and adult samples. We employ a new method to isolate and profile insulin-expressing cells and conclude that several different hPSC lines generate very similar insulin-expressing cells, cells whose transcripts resemble fetal rather than adult β cells. This study advances the possibility of directing the differentiation of stem cells into functional β cells by comparing and cataloging differences between hPSC-derived insulin-expressing cells and human β cells.
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“SC-islets generated in vitro remain transcriptionally and functionally immature compared to adult human islets.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [77]
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“This is a valid concern as fully reprogrammed iPSCs can be difficult to differentiate into mature adult cells and instead these differentiated cells often resemble their fetal counterparts (Hrvatin et al., 2014).”
From Multi-omic rejuvenation of human cells by maturation phase transient reprogramming (2022) · cites this paper as Hrvatin et al., 2014
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Cites
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“For example, pancreatic and duodenal homeobox 1 (PDX1), vmaf avian musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA), and NK6 homeobox 1 (NKX6-1) are markers of adult human β cells (17) and in vivo-matured hPSC-INS cells (22, 26).”
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Tissue-specific transcriptional regulation has diverged significantly between human and mouse
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Cited by
Sorted by citations
Generation of Functional Human Pancreatic β Cells In Vitro
Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.040 · Cited by 2,025
“We use the nomenclature PH (polyhormonal, Figure 1A) to refer to this cell population of in-vitro-differentiated hPSCs. Transcriptional analysis of in-vitro-differentiated PH cells showed that these cells resemble human fetal and not adult b cells (Hrvatin et al., 2014).”
BackgroundMethodInfluentialSelf-citationThe Journal of Clinical Investigation
Witkin, E. M. (2016) · Journal of the American Dietetic Association · doi:10.1016/0002-8223(94)92394-9 · Cited by 920
In vitro generation of human pluripotent stem cell derived lung organoids
Dye, B. R., Hill, D. R., Ferguson, M. A. H., Tsai, Y.-H., Nagy, M. S., Dyal, R., Wells, J. M., Mayhew, C. N., Nattiv, R., Klein, O. D., et al. (2015) · eLife · doi:10.7554/elife.05098 · Cited by 846
“DOI: 10.7554/eLife.05098 16 of 25 (Si-Tayeb et al., 2009; Hrvatin et al., 2014).”
InfluentialCharting cellular identity during human in vitro β-cell differentiation
Veres, A., Faust, A. L., Bushnell, H. L., Engquist, E. N., Kenty, J. H.-R., Harb, G., Poh, Y.-C., Sintov, E., Gürtler, M., Pagliuca, F. W., et al. (2019) · Nature · doi:10.1038/s41586-019-1168-5 · Cited by 552
Self-citationInduced Pluripotent Stem Cells Meet Genome Editing
Hockemeyer, D., & Jaenisch, R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.013 · Cited by 499
“For one, it became evident that many protocols that were developed for the differentiation of hPSCs into functional tissue resulted in embryonic rather than adult human cell types (Bedada et al., 2015; Forster et al., 2014; Hrvatin et al., 2014; Spence et al., 2011; Takebe et al., 2013).”
Background
Metadata
- Authors
- Hrvatin, S., O’Donnell, C. W., Deng, F., Millman, J. R., Pagliuca, F. W., DiIorio, P., Rezania, A., Gifford, D. K., & Melton, D. A.
- Affiliations
- Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute and
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Janssen Research & Development (United States) (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-02-10
- Volume
- 111
- Issue
- 8
- Pages
- 3038-3043
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3939927
- OpenAlex
- W2055001415
- Cited by
- 302
- References
- 0
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 19 · 2023: 30 · 2022: 25 · 2021: 33 · 2020: 42 · 2019: 15 · 2018: 18 · 2017: 15 · 2016: 47 · 2015: 25 · 2014: 8
- FWCI
- 31.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (U01HL100408, 1U01HL10040804)
- National Institute of Diabetes and Digestive and Kidney Diseases (RL1DK081184, 2U01DK07247307, U01DK072473)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- human pluripotent stem cells, pancreatic beta cells, fetal pancreas, gene expression profiling, stem cell differentiation, beta cell maturation, islet transplantation, gene expression signatures
- MeSH terms
- Adult, Cell Differentiation, Fetus, Flow Cytometry, Humans, Pancreas, Gene Expression Profiling, Pluripotent Stem Cells, Microarray Analysis, Insulin-Secreting Cells
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