Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation
Open accessAbstract
The in vitro differentiation of insulin-producing beta-like cells can model aspects of human pancreatic development. Here, we generate 95,308 single-cell transcriptomes and reconstruct a lineage tree of the entire differentiation process from human embryonic stem cells to beta-like cells to study temporally regulated genes during differentiation. We identify so-called 'switch genes' at the branch point of endocrine/non-endocrine cell fate choice, revealing insights into the mechanisms of differentiation-promoting reagents, such as NOTCH and ROCKII inhibitors, and providing improved differentiation protocols. Over 20% of all detectable genes are activated multiple times during differentiation, even though their enhancer activation is usually unimodal, indicating extensive gene reuse driven by different enhancers. We also identify a stage-specific enhancer at the TCF7L2 locus for diabetes, uncovered by genome-wide association studies, that drives a transient wave of gene expression in pancreatic progenitors. Finally, we develop a web app to visualize gene expression on the lineage tree, providing a comprehensive single-cell data resource for researchers studying islet biology and diabetes.
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Despite the use of different pluripotent stem cell lines and protocols, two scRNA-seq roadmaps observed well-known markers of pancreatic progenitors (e.g., PDX1, NKX6-1) during the middle stages of differentiation and islet-specific endocrine identity markers in their final cell populations.
“Despite the use of different pluripotent stem cell lines and protocols, both roadmaps observed well-known markers of pancreatic progenitors (e.g., PDX1, NKX6-1) during the middle stages of differentiation as well as islet-specific endocrine identity markers in their final cell populations (e.g., INS for β cells, GCG for α cells, SST for δ cells).”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredBoth scRNA-seq roadmaps detected significant cell diversification following the pancreatic progenitor stages.
“Interestingly, both scRNA-seq roadmaps detected significant cell diversification following the pancreatic progenitor stages.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
In Results, “A time-series single cell transcriptomic atlas during pancreatic β cell differentiation” (page unavailable), the paper says its cultures were relatively homogeneous before the pancreatic progenitor stage and much more heterogeneous later. It also reports cell populations found in an independent scRNA-seq dataset, but does not establish that both roadmaps detected diversification specifically after the pancreatic progenitor stage. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe final non-endocrine off-target populations, including duct-like and pancreatic stellate-like cells, branched during pancreatic progenitor stages.
“In contrast, the final non-endocrine off-target populations, including duct-like and pancreatic stellate-like cells, branched during pancreatic progenitor stages.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
NOTCH signaling via HES1 was implicated as a driver of a non-endocrine fate.
“Of note, NOTCH signaling via HES1 was implicated as a driver of a non-endocrine fate.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
1,150 endocrine-specific switch genes were identified, and it was inferred that 656 pairs of transcription factor and target gene interactions potentially influenced endocrine specification.
“1,150 endocrine-specific switch genes were identified, and it was inferred that 656 pairs of transcription factor and target gene interactions potentially influenced endocrine specification.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
The second report sequenced 87,769 cells across 12 points during the differentiation of a stem cell line known to result in highly heterogeneous SC-islets.
“The second report sequenced 87,769 cells across 12 points during the differentiation of a stem cell line known to result in highly heterogeneous SC-islets.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
SC-EC cells have been subsequently identified in SC-islets generated from various differentiation protocols and stem cell lines by multiple groups.
“These cells have been subsequently identified in SC-islets generated from various differentiation protocols and stem cell lines by multiple groups.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
Recent advances in single-cell sequencing technologies have allowed for unprecedented characterization of these cells to further elucidate ways to refine SC-β cell differentiation strategies.
“and recent advances in single-cell sequencing technologies have allowed for unprecedented characterization of these cells to further elucidate ways to refine SC-β cell differentiation strategies.43,47,50,51”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
Using a semi-supervised method to construct a lineage tree of cell fate, it was demonstrated that divergent cell populations that arose during early stages did not significantly contribute to the off-target populations observed later.
“Using a semi-supervised method to construct a lineage tree of cell fate, it was demonstrated that divergent cell populations that arose during early stages did not significantly contribute to the off-target populations observed later.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
Previous analysis of scRNA-seq data alone had suggested that SC-β and SC-EC are distinct cell types that share a common progenitor lineage during in vitro differentiation of SC-islets.
“Previous analysis of scRNA-seq data alone had suggested that SC-β and SC-EC are distinct cell types that share a common progenitor lineage during in vitro differentiation of SC-islets,”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [50]
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Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453 · see citing works
MEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648 · see citing works
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110 · see citing works
The single-cell transcriptional landscape of mammalian organogenesis
Cao, J., Spielmann, M., Qiu, X., Huang, X., Ibrahim, D. M., Hill, A. J., Zhang, F., Mundlos, S., Christiansen, L., Steemers, F. J., et al. (2019) · Nature · doi:10.1038/s41586-019-0969-x · Cited by 4,490 · see citing works
Buniello, A., MacArthur, J. A. L., Cerezo, M., Harris, L. W., Hayhurst, J., Malangone, C., McMahon, A., Morales, J., Mountjoy, E., Sollis, E., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1120 · Cited by 4,000 · see citing works
<b>NbClust</b> : An <i>R</i> Package for Determining the Relevant Number of Clusters in a Data Set
Charrad, M., Ghazzali, N., Boiteau, V., & Niknafs, A. (2014) · Journal of Statistical Software · doi:10.18637/jss.v061.i06 · Cited by 3,396 · see citing works
The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)
MacArthur, J., Bowler, E., Cerezo, M., Gil, L., Hall, P., Hastings, E., Junkins, H., McMahon, A., Milano, A., Morales, J., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1133 · Cited by 2,161 · see citing works
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 · see citing works
CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing
Labun, K., Montague, T. G., Krause, M., Cleuren, Y. N. T., Tjeldnes, H., & Valen, E. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz365 · Cited by 2,009 · see citing works
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O., Agulnick, A. D., Smart, N. G., Moorman, M. A., KROON, E. J., Carpenter, M. K., & Baetge, E. E. (2006) · Nature Biotechnology · doi:10.1038/nbt1259 · Cited by 1,913 · see citing works
Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., Young, H., Richardson, M., Smart, N. G., Cunningham, J., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1393 · Cited by 1,843 · see citing works
Mahajan, A., Taliun, D., Thurner, M., Robertson, N. R., Torres, J. M., Rayner, N. W., Payne, A. J., Steinthorsdottir, V., Scott, R. A., Grarup, N., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0241-6 · Cited by 1,744 · see citing works
Wolf, F. A., Hamey, F. K., Plass, M., Solana, J., Dahlin, J. S., Göttgens, B., Rajewsky, N., Simon, L., & Theis, F. J. (2019) · Genome Biology · doi:10.1186/s13059-019-1663-x · Cited by 1,698 · see citing works
A comparison of single-cell trajectory inference methods
Saelens, W., Cannoodt, R., Todorov, H., & Saeys, Y. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0071-9 · Cited by 1,670 · see citing works
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.3033 · Cited by 1,575 · see citing works
Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
Segerstolpe, Å., Palasantza, A., Eliasson, P., Andersson, E.-M., Andréasson, A.-C., Sun, X., Picelli, S., Sabirsh, A., Clausen, M., Bjursell, M. K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.020 · Cited by 1,550 · see citing works
Baron, M., Veres, A., Wolock, S. L., Faust, A. L., Gaujoux, R., Vetere, A., Ryu, J. H., Wagner, B. K., Shen-Orr, S. S., Klein, A. M., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.08.011 · Cited by 1,508 · see citing works
Notch signalling controls pancreatic cell differentiation
Apelqvist, Å., Li, H., Sommer, L., Beatus, P., Anderson, D. J., Honjo, T., de Angelis, M. H., Lendahl, U., & Edlund, H. (1999) · Nature · doi:10.1038/23716 · Cited by 1,158 · see citing works
Self-citationControl of endodermal endocrine development by Hes-1
Jensen, J. N., Pedersen, E. E., Galante, P. E., Hald, J., Heller, R. S., Ishibashi, M., Kageyama, R., Guillemot, F., Serup, P., & Madsen, O. D. (2000) · Nature Genetics · doi:10.1038/71657 · Cited by 1,155 · see citing works
Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations
Fulco, C. P., Nasser, J., Jones, T. R., Munson, G., Bergman, D. T., Subramanian, V., Grossman, S. R., Anyoha, R., Doughty, B. R., Patwardhan, T. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0538-0 · Cited by 1,111 · see citing works
Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
L. Lun, A. T., Bach, K., & Marioni, J. C. (2016) · Genome Biology · doi:10.1186/s13059-016-0947-7 · Cited by 1,108 · see citing works
Kulakovskiy, I. V., Vorontsov, I. E., Yevshin, I., Sharipov, R., Fedorova, A. D., Rumynskiy, E. I., Medvedeva, Y. A., Magana-Mora, A., Bajić, V. B., Papatsenko, D., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1106 · Cited by 921 · see citing works
Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes
Lyssenko, V., Lupi, R., Marchetti, P., Guerra, S. D., Orho‐Melander, M., Almgren, P., Sjögren, M., Ling, C., Eriksson, K., Lethagen, Υ.-L., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30706 · Cited by 821 · see citing works
Marked differences in differentiation propensity among human embryonic stem cell lines
Osafune, K., Caron, L., Borowiak, M., Martinez, R. J., Fitzgerald, C., Sato, Y., Cowan, C. A., Chien, K. R., & Melton, D. A. (2008) · Nature Biotechnology · doi:10.1038/nbt1383 · Cited by 815 · see citing works
Notch signaling controls multiple steps of pancreatic differentiation
Murtaugh, L. C., Stanger, B. Z., Kwan, K. M., & Melton, D. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436557100 · Cited by 782 · see citing works
Rezania, A., Bruin, J. E., Riedel, M. J., Mojibian, M., Asadi, A., Xu, J., Gauvin, R., Narayan, K., Karanu, F., O’Neil, J. J., et al. (2012) · Diabetes · doi:10.2337/db11-1711 · Cited by 582 · see citing works
Charting 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 · see citing works
Lawlor, N. T., George, J., Bolisetty, M. T., Kursawe, R., Sun, L., Vijayakumar, S., Kycia, I., Robson, P., & Stitzel, M. L. (2016) · Genome Research · doi:10.1101/gr.212720.116 · Cited by 540 · see citing works
The discovery of ribosome heterogeneity and its implications for gene regulation and organismal life
Genuth, N. R., & Barna, M. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.018 · Cited by 511 · see citing works
Segrè, A. V., DIAGRAM Consortium, MAGIC investigators, Groop, L., Mootha, V. K., Daly, M. J., & Altshuler, D. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001058 · Cited by 463 · see citing works
Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells
Velazco-Cruz, L., Song, J., Maxwell, K. G., Goedegebuure, M. M., Augsornworawat, P., Hogrebe, N. J., & Millman, J. R. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.12.012 · Cited by 399 · see citing works
Nostro, M. C., Sarangi, F., Ogawa, S., Holtzinger, A., Corneo, B., Li, X., Micallef, S. J., Park, I., Basford, C., Wheeler, M. B., et al. (2011) · Development · doi:10.1242/dev.055236 · Cited by 386 · see citing works
Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells
Hogrebe, N. J., Augsornworawat, P., Maxwell, K. G., Velazco-Cruz, L., & Millman, J. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0430-6 · Cited by 373 · see citing works
Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements
Gu, B., Swigut, T., Spencley, A., Bauer, M. R., Chung, M., Meyer, T., & Wysocka, J. (2018) · Science · doi:10.1126/science.aao3136 · Cited by 363 · see citing works
Kelly, O. G., Chan, M. Y., Martinson, L. A., Kadoya, K., Ostertag, T. M., Ross, K. G., Richardson, M., Carpenter, M. K., D'Amour, K. A., Kroon, E., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1931 · Cited by 348 · see citing works
Differentiated human stem cells resemble fetal, not adult, β cells
Hrvatin, S., O’Donnell, C. W., Deng, F., Millman, J. R., Pagliuca, F. W., DiIorio, P., Rezania, A., Gifford, D. K., & Melton, D. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400709111 · Cited by 302 · cited 1× · see citing works
“Synapse part (610) Regulation of secretion (699) Pancreatic beta cells (40) Neurotransmitter transport (155) Cell–cell signalling (767) Regulation of calcium ion transport into cytosol (92) Cellular response to fatty acid (51) Sodium channel regulator activity (32) Regulation of sodium transporter activity (38) Cation…”
DBD––taxonomically broad transcription factor predictions: new content and functionality
Wilson, D. A., Charoensawan, V., Kummerfeld, S., & Teichmann, S. A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm964 · Cited by 296 · see citing works
Wang, A., Yue, F., Li, Y., Xie, R., Harper, T. C., Patel, N. A., Muth, K., Palmer, J., Qiu, Y., Wang, J., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.02.013 · Cited by 263 · see citing works
Self-citationMaintaining embryonic stem cell pluripotency with Wnt signaling
Sokol, S. Y. (2011) · Development · doi:10.1242/dev.066209 · Cited by 257 · see citing works
Chiou, J., Zeng, C., Cheng, Z., Han, J. Y., Schlichting, M., Huang, S., Wang, J., Sui, Y., Deogaygay, A., Okino, M.-L., et al. (2019) · doi:10.1101/693671 · Cited by 189 · see citing works
Circadian Entrainment Triggers Maturation of Human In Vitro Islets
Alvarez-Dominguez, J. R., Donaghey, J., Rasouli, N., Kenty, J. H. R., Helman, A., Charlton, J., Straubhaar, J. R., Meissner, A., & Melton, D. A. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.11.011 · Cited by 189 · cited 3× · see citing works
“Interestingly, cell cycle genes (TOP2A, CENPE, MKI67, AURKB and CDK1) were not expressed in the entire endocrine lineage branch, indicating cell cycle exit during the fate choice to differentiate into pancreatic endocrine cells (module 57; Extended Data Fig.”
InfluentialLineage dynamics of murine pancreatic development at single-cell resolution
Byrnes, L. E., Wong, D. M., Subramaniam, M., Meyer, N. P., Gilchrist, C. L., Knox, S. M., Tward, A. D., Ye, C., & Sneddon, J. B. (2018) · Nature Communications · doi:10.1038/s41467-018-06176-3 · Cited by 185 · see citing works
Chiou, J., Zeng, C., Zhang, C., Han, J. Y., Schlichting, M., Miller, M., Mendez, R., Huang, S., Wang, J., Sui, Y., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00823-0 · Cited by 175 · see citing works
Lu, L., Liu, X., Huang, W., Giusti‐Rodríguez, P., Cui, J., Zhang, S., Xu, W., Wen, Z., Ma, S., Rosen, J. D., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.007 · Cited by 170 · see citing works
Self-citationRiedel, M. J., Asadi, A., Wang, R., Ao, Z., Warnock, G. L., & Kieffer, T. J. (2011) · Diabetologia · doi:10.1007/s00125-011-2344-9 · Cited by 166 · see citing works
Bruin, J. E., Erener, S., Vela, J., Hu, X., Johnson, J. D., Kurata, H., Lynn, F., Piret, J., Asadi, A., Rezania, A., et al. (2014) · Stem Cell Research · doi:10.1016/j.scr.2013.10.003 · Cited by 162 · see citing works
p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors
Georgia, S. K., Soliz, R., Li, M., Zhang, P., & Bhushan, A. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.05.036 · Cited by 153 · see citing works
Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D
Viñuela, A., Varshney, A., van de Bunt, M., Prasad, R. B., Asplund, O., Bennett, A., Boehnke, M., Brown, A. A., Erdos, M. R., Fadista, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18581-8 · Cited by 152 · see citing works
Xia, F., Xie, L., Mihic, A., Gao, X., Chen, Y., Gaisano, H. Y., & Tsushima, R. G. (2008) · Endocrinology · doi:10.1210/en.2008-0161 · Cited by 132 · see citing works
Bioinformatics construction of the human cell surfaceome
da Cunha, J. P. C., Galante, P. A. F., de Souza, J. E., de Souza, R. F., de Carvalho, P. M. B., Ohara, D. T., de Moura, R. P., Oba‐Shinjo, S. M., Marie, S. K. N., Silva, W. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907939106 · Cited by 131 · see citing works
Current Understanding on Role of the Wnt Signaling Pathway Effector TCF7L2 in Glucose Homeostasis
Jin, T. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1146 · Cited by 129 · see citing works
Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development
Sharon, N., Vanderhooft, J., Straubhaar, J., Mueller, J. W., Chawla, R., Zhou, Q., Engquist, E. N., Trapnell, C., Gifford, D. K., & Melton, D. A. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.083 · Cited by 125 · see citing works
Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes
Fang, Z., Weng, C., Li, H., Tao, R., Mai, W., Liu, X., Lu, L., Lai, S., Duan, Q., Álvarez‐González, C. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.043 · Cited by 124 · see citing works
Self-citationPlaisier, C. L., O’Brien, S. A., Bernard, B. M., Reynolds, S. M., Simon, Z., Toledo, C. M., Ding, Y., Reiss, D. J., Paddison, P. J., & Baliga, N. S. (2016) · Cell Systems · doi:10.1016/j.cels.2016.06.006 · Cited by 116 · see citing works
A Rising Star in Pancreatic Diseases: Pancreatic Stellate Cells
Xue, R., Jia, K., Wang, J., Yang, L., Wang, Y., Gao, L., & Hao, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00754 · Cited by 112 · see citing works
Single-Cell Transcriptome Profiling of Mouse and hESC-Derived Pancreatic Progenitors
Krentz, N. A. J., Lee, M. Y. Y., Xu, E. E., Sproul, S. L. J., Maslova, A., Sasaki, S., & Lynn, F. C. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.11.008 · Cited by 111 · see citing works
Scavuzzo, M. A., Hill, M. C., Chmielowiec, J., Yang, D., Teaw, J., Sheng, K., Kong, Y., Bettini, M., Zong, C. C., Martin, J. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05740-1 · Cited by 91 · see citing works
ROCKII inhibition promotes the maturation of human pancreatic beta-like cells
Ghazizadeh, Z., Kao, D.-I., Amin, S., Cook, B. D., Rao, S. D., Zhou, T., Zhang, T., Xiang, Z.-Y., Kenyon, R., Kaymakcalan, O. E., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00129-y · Cited by 88 · see citing works
Pimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control
Gerst, J. E. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.08.004 · Cited by 73 · see citing works
Involvement of Rho/Rho kinase pathway in regulation of apoptosis in rat hepatic stellate cells
Ikeda, H., Nagashima, K., Yanase, M., Tomiya, T., Arai, M., Inoue, Y., Tejima, K., Nishikawa, T., Omata, M., Kimura, S., et al. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00039.2003 · Cited by 66 · see citing works
Tsuchiya, M., Hosaka, M., Moriguchi, T., Zhang, S., Suda, M., Yokota‐Hashimoto, H., Shinozuka, K., & Takeuchi, T. (2010) · Endocrinology · doi:10.1210/en.2010-0623 · Cited by 57 · see citing works
He, K. H. H., Lorenzo, P. I., Brun, T., Moreno, C. M. J., Aeberhard, D., Ortega, J. V., Cornu, M., Thorel, F., Gjinovci, A., Thorens, B., et al. (2011) · Diabetes · doi:10.2337/db10-1102 · Cited by 56 · see citing works
Post-transcriptional regulation of the pluripotent state
Chen, Q., & Hu, G. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.06.010 · Cited by 35 · see citing works
A transcriptomic roadmap to α- and β-cell differentiation in the embryonic pancreas
van Gurp, L., Muraro, M. J., Dielen, T., Seneby, L., Dharmadhikari, G., Gradwohl, G., van Oudenaarden, A., & de Koning, E. J. P. (2019) · Development · doi:10.1242/dev.173716 · Cited by 34 · see citing works
Bailey, K. A., Savic, D., Zielinski, M. C., Park, S. Y., Wang, L., Witkowski, P., Brady, M., Hara, M., Bell, G. I., & Nóbrega, M. A. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu577 · Cited by 30 · see citing works
Perez‐Alcantara, M., Honoré, C., Wesolowska‐Andersen, A., Gloyn, A. L., McCarthy, M. I., Hansson, M. D., Beer, N. L., & van de Bunt, M. (2018) · Diabetologia · doi:10.1007/s00125-018-4612-4 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [49]Viñuela A Influence of genetic variants on gene expression in human pancreatic islets - implications for type 2 diabetes. bioRxiv, doi:doi: 10.1101/655670 (2019). · DOI
Cited by
Sorted by citations
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210 · see citing works
Engineering islets from stem cells for advanced therapies of diabetes
Siehler, J., Blöchinger, A. K., Meier, M., & Lickert, H. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00262-w · Cited by 125 · see citing works
Augsornworawat, P., Hogrebe, N. J., Ishahak, M., Schmidt, M. D., Marquez, E., Maestas, M. M., Veronese-Paniagua, D., Gale, S. E., Miller, J. R., Velazco-Cruz, L., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01150-8 · Cited by 85 · see citing works
Zhu, H., Wang, G., Nguyen-Ngoc, K.-V., Kim, D., Miller, M., Goss, G., Kovsky, J., Harrington, A. R., Saunders, D. C., Hopkirk, A. L., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.03.011 · Cited by 85 · see citing works
Wakeling, M. N., Owens, N. D. L., Hopkinson, J. R., Johnson, M. B., Houghton, J., Dastamani, A., Flaxman, C. S., Wyatt, R. C., Hewat, T. I., Hopkins, J. J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01204-x · Cited by 66 · see citing works
Islet organoid as a promising model for diabetes
Zhang, X., Ma, Z., Song, E., & Xu, T. (2021) · Protein & Cell · doi:10.1007/s13238-021-00831-0 · Cited by 52 · see citing works
Advances in Cell Replacement Therapies for Diabetes
Hering, B. J., Rickels, M. R., Bellin, M. D., Millman, J. R., Tomei, A. A., Garcı́a, A. J., Shirwan, H., Stabler, C. L., Ma, M., Peng, Y., et al. (2025) · Diabetes · doi:10.2337/db25-0037 · Cited by 49 · see citing works
Extensive NEUROG3 occupancy in the human pancreatic endocrine gene regulatory network
Schreiber, V., Mercier, R., Jiménez, S., Ye, T., García-Sánchez, E., Klein, A.-C., Meunier, A., Ghimire, S., Birck, C., Jost, B., et al. (2021) · bioRxiv · doi:10.1016/j.molmet.2021.101313 · Cited by 34 · see citing works
Lessons from single-cell RNA sequencing of human islets
Ngara, M., & Wierup, N. (2022) · Diabetologia · doi:10.1007/s00125-022-05699-1 · Cited by 35 · see citing works
Embryonic macrophages support endocrine commitment during human pancreatic differentiation
Migliorini, A., Ge, S., Atkins, M. H., Oakie, A., Sambathkumar, R., Kent, G., Huang, H., Sing, A., Chua, C., Gehring, A. J., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.09.011 · Cited by 31 · see citing works
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · BMC Genomics · doi:10.1186/s12864-024-10013-x · Cited by 30 · see citing works
Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells
Jin, W., & Jiang, W. (2022) · Cell Regeneration · doi:10.1186/s13619-022-00125-8 · Cited by 25 · see citing works
Parveen, N., Wang, J. K., Bhattacharya, S., Cuala, J., Rajkumar, M. S., Butler, A. E., Wu, X., Shih, H.-P., Georgia, S. K., & Dhawan, S. (2023) · Diabetes · doi:10.2337/db22-0506 · Cited by 23 · see citing works
He, W., Rebello, O. D., Henne, A., Nikolka, F., Klein, T., & Maedler, K. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.697120 · Cited by 22 · see citing works
Yang, J., Yan, Y., Yin, X.-Y., Liu, X.-Q., Reshetov, I., Karalkin, P., Li, Q.-F., & Huang, R.-L. (2024) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2024.155786 · Cited by 20 · see citing works
The human α cell in health and disease
Pettway, Y. D., Saunders, D. C., & Briššová, M. (2023) · Journal of Endocrinology · doi:10.1530/joe-22-0298 · Cited by 20 · see citing works
Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation
Sanavia, T., Huang, C., Manduchi, E., Xu, Y., Dadi, P., Potter, L. A., Jacobson, D., Camillo, B. D., Magnuson, M., Stoeckert, C., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.648791 · Cited by 13 · see citing works
Heterogeneous enhancer states orchestrate β cell responses to metabolic stress
Wang, L., Wu, J., Sramek, M., Obayomi, S. M. B., Gao, P., Li, Y., Matveyenko, A. V., & Wei, Z. (2024) · Nature Communications · doi:10.1038/s41467-024-53717-0 · Cited by 17 · see citing works
Self-citationBraam, M., Zhao, J., Liang, S., Ida, S., Kloostra, N. K., Iworima, D., Tang, M., Baker, R. K., Quiskamp, N., Piret, J., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-35716-1 · Cited by 18 · see citing works
Lin, L., Zhang, Y., Qian, W., Liu, Y., Zhang, Y., Lin, F., Liu, C., Lu, G., Sun, D., Guo, X., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119767119 · Cited by 16 · see citing works
FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection
Meng, H., Liao, Z., Ji, Y., Wang, D., Yang, H. K., Huang, C., Hu, X., Chen, J., Zhang, H., Li, Z., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01790-8 · Cited by 15 · see citing works
SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
Szlachcic, W. J., Dąbrowska, A., Milewska, A., Ziojla, N., Błaszczyk, K., Barreto-Durán, E., Sanak, M., Surmiak, M., Owczarek, K., Grzanka, D., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104594 · Cited by 15 · see citing works
Hiyoshi, H., Sakuma, K., Asano, S., Napier, S. C., Konagaya, S., Mochida, T., Ueno, H., Watanabe, T., Kassai, Y., Matsumoto, H., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2320883121 · Cited by 12 · see citing works
Aldous, N., Elsayed, A. K., Memon, B., Ijaz, S., Hayat, S., & Abdelalim, E. M. (2024) · Diabetologia · doi:10.1007/s00125-024-06232-2 · Cited by 13 · see citing works
Bartolomé, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010501 · Cited by 13 · see citing works
m6A mRNA methylation by METTL14 regulates early pancreatic cell differentiation
Kahraman, S., Jesus, D. F. D., Wei, J., Brown, N. K., Zou, Z., Hu, J. Y., Pirouz, M., Gregory, R. I., He, C., & Kulkarni, R. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00213-2 · Cited by 12 · see citing works
Goode, R. A., Hum, J. M., & Kalwat, M. A. (2022) · Endocrinology · doi:10.1210/endocr/bqac193 · Cited by 11 · see citing works
Characterization of cell-fate decision landscapes by estimating transcription factor dynamics
Jiménez, S., Schreiber, V., Mercier, R., Gradwohl, G., & Molina, N. (2022) · bioRxiv · doi:10.1016/j.crmeth.2023.100512 · Cited by 9 · see citing works
FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction
Tacto, C., Tahbaz, M., Salib, A., Wang, S., Cayabyab, F., Choi, J., Kim, K. A., Hamba, Y., Perez, H. D., Gershon, P. D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60188-4 · Cited by 8 · see citing works
Wei, Y., Hong, F., Xie, S., Luo, X., Li, X., Dao, F., Deng, K., Lin, H., & Lv, H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262211005 · Cited by 8 · see citing works
ETVs dictate hPSC differentiation by tuning biophysical properties
Ziojła, N. M., Socha, M., Guerra, M. C., Kizewska, D. K., Blaszczyk, K., Urbaniak, E., Henry, S., Grabowska, M., Niakan, K. K., Warmflash, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56591-6 · Cited by 6 · see citing works
Yang, L., Yu, X.-X., Wang, X., Jin, C.-T., & Xu, C.-R. (2025) · Science Advances · doi:10.1126/sciadv.adt4770 · Cited by 7 · see citing works
Veronese-Paniagua, D., Maestas, M. M., Hernandez-Rincon, D. C., Hinshaw, K. E., Ishahak, M., Taylor, J. P., Tse, H. M., & Millman, J. R. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116211 · Cited by 7 · see citing works
Li, Y., Xu, M.-Q., Chen, J.-L., Huang, J.-S., Cao, J.-Y., Chen, H., Zhang, J., Luo, Y.-K., Wang, Y.-Z., & Sun, J. (2024) · Stem cell research & therapeutics · doi:10.1186/s13287-024-03780-7 · Cited by 5 · see citing works
Self-citationControlling Human Stem Cell‐Derived Islet Composition Using Magnetic Sorting
Kelley, A. B., Shunkarova, M., Maestas, M. M., Gale, S. E., Mukherjee, N., Hogrebe, N. J., & Millman, J. R. (2025) · Biotechnology and Bioengineering · doi:10.1002/bit.29030 · Cited by 6 · see citing works
Laver, T. W., Wakeling, M. N., Caswell, R. C., Bunce, B., Yau, D., Männistö, J. M. E., Houghton, J., Hopkins, J. J., Weedon, M. N., Saraff, V., et al. (2024) · European Journal of Human Genetics · doi:10.1038/s41431-024-01593-z · Cited by 7 · see citing works
Temporal single-cell regeneration studies: the greatest thing since sliced pancreas?
Domínguez‐Bendala, J., Qadir, M. M. F., & Pastori, R. L. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.009 · Cited by 8 · see citing works
Improving stem cell-derived pancreatic islets using single-cell multiome-inferred regulomes
Zhu, H., Wang, G., Nguyen-Ngoc, K.-V., Kim, D., Miller, M., Goss, G., Kovsky, J., Harrington, A. R., Saunders, D., Melton, R., et al. (2022) · doi:10.1101/2022.09.25.509355 · Cited by 85 · see citing works
Bridging the variant-to-function gap in type 2 diabetes: advances and challenges
Maynard, A. G., Bhardwaj, R., Jones, T. R., & Claussnitzer, M. (2025) · Diabetologia · doi:10.1007/s00125-025-06600-6 · Cited by 6 · see citing works
Veronese-Paniagua, D., & Millman, J. R. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1734431 · Cited by 5 · see citing works
Fang, X., Zhang, Y., Miao, R., Zhang, Y., Yin, R., Guan, H., Huang, X., & Tian, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116292 · Cited by 4 · see citing works
Ning, H., Horikawa, A., Yamamoto, T., & Michiue, T. (2023) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-023-00776-0 · Cited by 4 · see citing works
Hogrebe, N. J., Schmidt, M. D., Augsornworawat, P., Gale, S. E., Shunkarova, M., & Millman, J. R. (2026) · Nature Communications · doi:10.1038/s41467-026-71324-z · Cited by 5 · see citing works
In Situ Visualizing Nascent RNA by Exploring DNA-Templated Oxidative Amination of 4-Thiouridine
Shang, J., He, L., Wang, J., Tong, A., & Xiang, Y. (2021) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.1c00524 · Cited by 3 · see citing works
Mima, A., Kimura, A., Ito, R., Hatano, Y., Tsujimoto, H., Mae, S.-I., Yamane, J., Fujibuchi, W., Uza, N., Toyoda, T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-88690-1 · Cited by 4 · see citing works
Predictive control of human pancreatic cell fate using a digital model of in vitro differentiationPreprint
Sanchez-Castro, E. E., Ishahak, M., Le, T., Maestas, M. M., Hernandez-Rincon, D. C., Mukherjee, N., Bradley, K., Lu, J., Gale, S. E., & Millman, J. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.27.721124 · Cited by 3 · see citing works
Modeling immune responses to autologous and allogeneic human stem cell–derived islet grafts in vivo
Genzano, C. B., Zanetti, G., Du, Traum, D., Lahori, D., Downes, G. M., Bhatele, S., Ding, X., Apley, K. D., Firdessa-Fite, R., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.200738 · Cited by 2 · see citing works
Safety Issues Related to Pluripotent Stem Cell-Based Therapies: Tumour Risk
Hillenius, S., Montilla‐Rojo, J., Eleveld, T. F., Salvatori, D. C. F., & Looijenga, L. H. J. (2023) · Springer eBooks · doi:10.1007/978-3-031-41943-0_18 · Cited by 2 · see citing works
TCF7 is not essential for glucose homeostasis in mice
Kaur, K. D., Wong, C. K., Baggio, L. L., Beaudry, J. L., Fuchs, S., Panaro, B. L., Matthews, D., Cao, X., & Drucker, D. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101213 · Cited by 2 · see citing works
Hogrebe, N. J., Schmidt, M. D., Augsornworawat, P., Gale, S. E., Shunkarova, M., & Millman, J. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.21.618465 · Cited by 2 · see citing works
Divergent cell-type specific hypoxia responses in human stem cell-derived and primary islets
Bradley, K., Moore, C., Ishahak, M., Maestas, M. M., Veronese-Paniagua, D., & Millman, J. R. (2026) · Scientific Reports · doi:10.1038/s41598-026-52074-w · Cited by 1 · see citing works
Stem cell therapies for treatment of diabetes mellitus
Guo, F., Song, Y., & Qin, G. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004150 · Cited by 1 · see citing works
Ratiu, J. J., Southard, S. M., & Rust, W. L. (2023) · Medical Research Archives · doi:10.18103/mra.v11i12.4797 · Cited by 1 · see citing works
m 6 A mRNA Methylation Regulates Early Pancreatic β-Cell DifferentiationPreprint
Kahraman, S., Jesus, D. F. D., Wei, J., Brown, N. K., Zou, Z., Hu, J. Y., He, C., & Kulkarni, R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.03.551675 · Cited by 1 · see citing works
Yu, T., XinYi, C. H. E. N., Cissy Qing, Y. U., & Arial Yi, Z. E. N. G. (2022) · Scientia Sinica Vitae · doi:10.1360/ssv-2022-0031
Ratiu, J. J., Southard, S., & Rust, W. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.20.563345
Mimicking Islet Development with Human Pluripotent Stem Cells
Faust, A. L., Veres, A., & Melton, D. A. (2023) · Springer eBooks · doi:10.1007/978-3-031-41943-0_1
Aldous, N., Elsayed, A. K., Memon, B., Ijaz, S., Hayat, S., & Abdelalim, E. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.06.583663
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672244
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672247
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672262
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672250
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672259
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672256
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672253
Veronese-Paniagua, D., Banks, C. E., Bradley, K., Mukherjee, N., Gale, S. E., Hinshaw, K. E., Meacham, A. M., Iwaloye, O. F., Tse, H. M., Mathews, C. E., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.30.697107
Dysregulated autophagy at the nexus of type 2 diabetes mellitus and pancreatic cancer pathogenesis
Li, L., Chen, Y., Wang, S., Du, W., Lao, T., Chen, F., Yao, G., Chen, W., Li, X., Liu, C., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1735726
Chen, G., Ma, X., Jiang, L., Zhou, Z., Li, Q., Deng, Q., Li, Y., He, Y., Wang, Y., Wang, X., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.116990
Self-citationJabri, A., Alsharif, M., Taftafa, B., Abbad, T., Sibai, D., Mhannayeh, A., Elsalti, A., Saadeldin, I. M., Salma, J., Mir, T. A., et al. (2026) · Bioengineering · doi:10.3390/bioengineering13040478 · Cited by 1 · see citing works
Move BeTween modAlities (MBTA) employs flow matching to predict single cell data modalitiesPreprint
Xu, B., Zhang, Y., & Michor, F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.05.743110
Veronese-Paniagua, D., Banks, C. E., Bradley, K., Mukherjee, N., Gale, S. E., Hinshaw, K. E., Meacham, A. M., Iwaloye, O. F., Tse, H. M., Mathews, C. E., et al. (2026) · iScience · doi:10.1016/j.isci.2026.117560
- Authors
- Weng, C., Xi, J., Li, H., Cui, J., Gu, A., Lai, S., Leskov, K., Ke, L., Jin, F., & Li, Y.
- Affiliations
- Case Western Reserve University (US)
- Case Comprehensive Cancer Center (US)
- Corresponding author
- Jin, Fulai
- Li, Yan
- Venue
- Nature Metabolism
- Published
- 2020-11-30
- Volume
- 2
- Issue
- 12
- Pages
- 1443-1458
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC7744443
- OpenAlex
- W3107485993
- Cited by
- 65
- References
- 67
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 8
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mount Sinai Health System (OSA510113, OSA510114)
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (R01HG009658)
- Case Western Reserve University (VSN639001)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01DK113185)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- beta cell differentiation, human embryonic stem cells, single-cell transcriptomics, lineage trees, switch genes, TCF7L2, pancreatic progenitors, Notch inhibitors, diabetes mellitus, differentiation protocols, gene expression waves
- MeSH terms
- Transcription Factor HES-1, Insulin Secretion, Cell Differentiation, Diabetes Mellitus, Genes, Switch, Glucose, Humans, Gene Expression Regulation, Developmental, Cell Lineage, Insulin-Secreting Cells, Embryonic Stem Cells, Gene Knockdown Techniques, Transcription Factor 7-Like 2 Protein
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