In-organoid single-cell CRISPR screening reveals determinants of hepatocyte differentiation and maturation
Open accessAbstract
Background: Harnessing hepatocytes for basic research and regenerative medicine demands a complete understanding of the genetic determinants underlying hepatocyte differentiation and maturation. Single-cell CRISPR screens in organoids could link genetic perturbations with parallel transcriptomic readout in single cells, providing a powerful method to delineate roles of cell fate regulators. However, a big challenge for identifying key regulators during data analysis is the low expression levels of transcription factors (TFs), which are difficult to accurately estimate due to noise and dropouts in single-cell sequencing. Also, it is often the changes in TF activities in the transcriptional cascade rather than the expression levels of TFs that are relevant to the cell fate transition. Results: Here, we develop Organoid-based Single-cell CRISPR screening Analyzed with Regulons (OSCAR), a framework using regulon activities as readouts to dissect gene knockout effects in organoids. In adult-stem-cell-derived liver organoids, we map transcriptomes in 80,576 cells upon 246 perturbations associated with transcriptional regulation of hepatocyte formation. Using OSCAR, we identify known and novel positive and negative regulators, among which Fos and Ubr5 are the top-ranked ones. Further single-gene loss-of-function assays demonstrate that Fos depletion in mouse and human liver organoids promote hepatocyte differentiation by specific upregulation of liver metabolic genes and pathways, and conditional knockout of Ubr5 in mouse liver delays hepatocyte maturation. Conclusions: Altogether, we provide a framework to explore lineage specifiers in a rapid and systematic manner, and identify hepatocyte determinators with potential clinical applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CRISPR cutting screens in 3D organoids have been implemented to explore factors such as growth factor dependency for cell growth, identify potential cancer-driving forces, and uncover key genetic events in cell differentiation.
“Even more exciting is the implementation of CRISPR cutting screens in 3D organoids to explore factors such as growth factor dependency for cell growth14–16, identifying potential cancer-driving forces17–19, and uncovering key genetic events in cell differentiation20–22.”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dixit, A., Parnas, O., Li, B., Chen, J., Fulco, C. P., Jerby-Arnon, L., Marjanovic, N. D., Dionne, D., Burks, T., Raychowdhury, R., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.038 · Cited by 1,863 · see citing works
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619 · see citing works
Adamson, B., Norman, T. M., Jost, M., Cho, M. Y., Nuñez, J. K., Chen, Y., Villalta, J. E., Gilbert, L. A., Horlbeck, M. A., Hein, M. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.048 · Cited by 1,193 · see citing works
Pooled CRISPR screening with single-cell transcriptome readout.
Datlinger, P., Rendeiro, A. F., Schmidl, C., Krausgruber, T., Traxler, P., Klughammer, J., Schuster, L. C., Kuchler, A., Alpar, D., & Bock, C. (2017) · Nature Methods · doi:10.1038/nmeth.4177 · Cited by 1,096 · see citing works
Hippo Pathway Activity Influences Liver Cell Fate
Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857 · see citing works
Broutier, L., Andersson-Rolf, A., Hindley, C. J., Boj, S. F., Clevers, H., Koo, B.-K., & Huch, M. (2016) · Nature Protocols · doi:10.1038/nprot.2016.097 · Cited by 834 · see citing works
Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
Raven, A., Lu, W.-Y., Man, T. Y., Ferreira-Gonzalez, S., O’Duibhir, E., Dwyer, B. J., Thomson, J. P., Meehan, R. R., Bogorad, R., Koteliansky, V., et al. (2017) · Nature · doi:10.1038/nature23015 · Cited by 533 · see citing works
Holland, C. H., Tanevski, J., Perales-Patón, J., Gleixner, J., Kumar, M. P., Mereu, E., Joughin, B. A., Stegle, O., Lauffenburger, D. A., Heyn, H., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-1949-z · Cited by 323 · see citing works
Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids
Marsee, A., Roos, F. J. M., Verstegen, M. M. A., Marsee, A., Roos, F., Verstegen, M., Clevers, H., Vallier, L., Takebe, T., Huch, M., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.005 · Cited by 310 · see citing works
Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes
Deng, X., Zhang, X., Li, W., Feng, R.-X., Li, L., Yi, G.-R., Zhang, X.-N., Yin, C., Yu, H.-Y., Zhang, J.-P., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.05.022 · Cited by 289 · see citing works
Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks
Knutson, S. K., Chyla, B. J., Amann, J. M., Bhaskara, S., Huppert, S. S., & Hiebert, S. W. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.51 · Cited by 271 · see citing works
Pepe-Mooney, B. J., Dill, M. T., Alemany, A., Ordovas-Montanes, J., Matsushita, Y., Rao, A., Sen, A., Miyazaki, M., Anakk, S., Dawson, P. A., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.004 · Cited by 266 · see citing works
On the design of CRISPR-based single-cell molecular screens
Hill, A. J., McFaline-Figueroa, J. L., Starita, L. M., Gasperini, M. J., Matreyek, K. A., Packer, J., Jackson, D., Shendure, J., & Trapnell, C. (2018) · Nature Methods · doi:10.1038/nmeth.4604 · Cited by 262 · see citing works
Planas-Paz, L., Sun, T., Pikiolek, M., Cochran, N. R., Bergling, S., Orsini, V., Yang, Z., Sigoillot, F., Jetzer, J., Syed, M., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.005 · Cited by 216 · see citing works
scMAGeCK links genotypes with multiple phenotypes in single-cell CRISPR screens
Yang, L., Zhu, Y., Yu, H., Cheng, X., Chen, S., Chu, Y., Huang, H., Zhang, J., & Li, W. (2020) · Genome Biology · doi:10.1186/s13059-020-1928-4 · Cited by 94 · see citing works
Murakami, K., Terakado, Y., Saito, K., Jomen, Y., Takeda, H., Oshima, M., & Barker, N. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016806118 · Cited by 62 · see citing works
Direct-seq: programmed gRNA scaffold for streamlined scRNA-seq in CRISPR screen
Song, Q., Ni, K., Liu, M., Li, Y., Wang, L., Wang, Y., Liu, Y., Yu, Z., Qi, Y., Lu, Z., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-02044-w · Cited by 26 · see citing works
Signalling pathways and transcriptional regulators orchestrating liver development and cancer
Campbell, S. A., Stephan, T. L., Lotto, J., Cullum, R., Drissler, S., & Hoodless, P. A. (2021) · Development · doi:10.1242/dev.199814 · Cited by 22 · cited 3× · see citing works
“Tcf7l2/Tcf4 acts as the transcriptional partner with β-catenin at the downstream of Wnt signaling, which is also required for liver development and the postnatal proliferation of hepatocytes [2, 33].”
Background
Flagged first, then by citations
Research works printed but not linked: 42
- [1]Itoh T Stem/progenitor cells in liver regeneration Hepatology 2016 64 663 668 10.1002/hep.28661 27227904 · DOI
- [5]Rodrigo-Torres D Affo S Coll M Morales-Ibanez O Millan C Blaya D Alvarez-Guaita A Rentero C Lozano JJ Maestro MA The Biliary Epithelium Gives Rise to Liver Progenitor Cells Hepatology 2014 60 1367 1377 10.1002/hep.27078 24700364 PMC4410184 · DOI · Paper page
- [6]Si-Tayeb K Noto FK Nagaoka M Li J Battle MA Duris C North PE Dalton S Duncan SA Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells Hepatology 2010 51 297 305 10.1002/hep.23354 19998274 PMC2946078 · DOI · Paper page
- [7]Hannan NR Segeritz CP Touboul T Vallier L Production of hepatocyte-like cells from human pluripotent stem cells Nat Protoc 2013 8 430 437 10.1038/nprot.2012.153 23424751 PMC3673228 · DOI
- [8]Wang X Yang L Wang YC Xu ZR Feng Y Zhang J Wang Y Xu CR Comparative analysis of cell lineage differentiation during hepatogenesis in humans and mice at the single-cell transcriptome level Cell Res 2020 30 1109 1126 10.1038/s41422-020-0378-6 32690901 PMC7784864 · DOI
- [9]Wesley BT Ross ADB Muraro D Miao Z Saxton S Tomaz RA Morell CM Ridley K Zacharis ED Petrus-Reurer S Single-cell atlas of human liver development reveals pathways directing hepatic cell fates Nat Cell Biol 2022 24 1487 1498 10.1038/s41556-022-00989-7 36109670 PMC7617064 · DOI · Paper page
- [10]Li M Izpisua Belmonte JC Organoids - Preclinical Models of Human Disease N Engl J Med 2019 380 569 579 10.1056/NEJMra1806175 30726695 · DOI
- [12]Huch M Dorrell C Boj SF van Es JH Li VS van de Wetering M Sato T Hamer K Sasaki N Finegold MJ In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration Nature 2013 494 247 250 10.1038/nature11826 23354049 PMC3634804 · DOI · Paper page
- [15]Wei J Ran G Wang X Jiang N Liang J Lin X Ling C Zhao B Gene manipulation in liver ductal organoids by optimized recombinant adeno-associated virus vectors J Biol Chem 2019 294 14096 14104 10.1074/jbc.RA119.008616 31366731 PMC6755792 · DOI
- [19]Jaitin DA Weiner A Yofe I Lara-Astiaso D Keren-Shaul H David E Salame TM Tanay A van Oudenaarden A Amit I Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq Cell 2016 167 1883 1896 e1815 10.1016/j.cell.2016.11.039 27984734 · DOI · Paper page
- [21]Xie S Duan J Li B Zhou P Hon GC Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single Cells Mol Cell 2017 66 285 299 e285 10.1016/j.molcel.2017.03.007 28416141 · DOI · Paper page
- [25]Platt RJ Chen S Zhou Y Yim MJ Swiech L Kempton HR Dahlman JE Parnas O Eisenhaure TM Jovanovic M CRISPR-Cas9 knockin mice for genome editing and cancer modeling Cell 2014 159 440 455 10.1016/j.cell.2014.09.014 25263330 PMC4265475 · DOI · Paper page
- [27]Li S Li M Liu X Yang Y Wei Y Chen Y Qiu Y Zhou T Feng Z Ma D Genetic and Chemical Screenings Identify HDAC3 as a Key Regulator in Hepatic Differentiation of Human Pluripotent Stem Cells Stem Cell Reports 2018 11 22 31 10.1016/j.stemcr.2018.05.001 29861165 PMC6066908 · DOI
- [28]Bhate A Parker DJ Bebee TW Ahn J Arif W Rashan EH Chorghade S Chau A Lee JH Anakk S ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation Nat Commun 2015 6 8768 10.1038/ncomms9768 26531099 PMC4635967 · DOI · Paper page
- [29]Clotman F Lannoy VJ Reber M Cereghini S Cassiman D Jacquemin P Roskams T Rousseau GG Lemaigre FR The onecut transcription factor HNF6 is required for normal development of the biliary tract Development 2002 129 1819 1828 10.1242/dev.129.8.1819 11934848 · DOI
- [30]Kaji K Factor VM Andersen JB Durkin ME Tomokuni A Marquardt JU Matter MS Hoang T Conner EA Thorgeirsson SS DNMT1 Is a Required Genomic Regulator for Murine Liver Histogenesis and Regeneration Hepatology 2016 64 582 598 10.1002/hep.28563 26999257 PMC5841553 · DOI · Paper page
- [31]Parviz F Matullo C Garrison WD Savatski L Adamson JW Ning G Kaestner KH Rossi JM Zaret KS Duncan SA Hepatocyte nuclear factor 4 alpha controls the development of a hepatic epithelium and liver morphogenesis Nat Genet 2003 34 292 296 10.1038/ng1175 12808453 · DOI · Paper page
- [32]Reizel Y Sabag O Skversky Y Spiro A Steinberg B Bernstein D Wang A Kieckhaefer J Li C Pikarsky E Postnatal DNA demethylation and its role in tissue maturation Nat Commun 2018 9 2040 10.1038/s41467-018-04456-6 29795194 PMC5966414 · DOI · Paper page
- [34]Jin X, Simmons SK, Guo A, Shetty AS, Ko M, Nguyen L, Jokhi V, Robinson E, Oyler P, Curry N, et al. In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes. Science 2020, 370. PMC7985844 33243861
- [35]Aibar S Gonzalez-Blas CB Moerman T Huynh-Thu VA Imrichova H Hulselmans G Rambow F Marine JC Geurts P Aerts J SCENIC: single-cell regulatory network inference and clustering Nat Methods 2017 14 1083 1086 10.1038/nmeth.4463 28991892 PMC5937676 · DOI · Paper page
- [36]Odom DT Zizlsperger N Gordon DB Bell GW Rinaldi NJ Murray HL Volkert TL Schreiber J Rolfe PA Gifford DK Control of pancreas and liver gene expression by HNF transcription factors Science 2004 303 1378 1381 10.1126/science.1089769 14988562 PMC3012624 · DOI
- [37]Westmacott A Burke ZD Oliver G Slack JM Tosh D C/EBPalpha and C/EBPbeta are markers of early liver development Int J Dev Biol 2006 50 653 657 10.1387/ijdb.062146aw 16892179 PMC2816035 · DOI
- [38]Sun L Cai J Gonzalez FJ The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer Nat Rev Gastroenterol Hepatol 2021 18 335 347 10.1038/s41575-020-00404-2 33568795 · DOI
- [39]Pawlak M Lefebvre P Staels B Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease J Hepatol 2015 62 720 733 10.1016/j.jhep.2014.10.039 25450203 · DOI · Paper page
- [42]Li M Belmonte JCL Organoids - Preclinical Models of Human Disease Reply N Engl J Med 2019 380 1982 1982 10.1056/NEJMra1806175 31091397 · DOI
- [43]Yang L Wang WH Qiu WL Guo Z Bi E Xu CR A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation Hepatology 2017 66 1387 1401 10.1002/hep.29353 28681484 PMC5650503 · DOI
- [44]Bakiri L Hamacher R Grana O Guio-Carrion A Campos-Olivas R Martinez L Dienes HP Thomsen MK Hasenfuss SC Wagner EF Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation J Exp Med 2017 214 1387 1409 10.1084/jem.20160935 28356389 PMC5413325 · DOI
- [45]Volk A Liang K Suraneni P Li X Zhao J Bulic M Marshall S Pulakanti K Malinge S Taub J A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis Cancer Cell 2018 34 707 723 e707 10.1016/j.ccell.2018.10.004 30423293 PMC6235627 · DOI
- [46]Liu B Jing Z Zhang X Chen Y Mao S Kaundal R Zou Y Wei G Zang Y Wang X Large-scale multiplexed mosaic CRISPR perturbation in the whole organism Cell 2022 185 3008 3024 e3016 10.1016/j.cell.2022.06.039 35870449 · DOI
- [47]Esk C Lindenhofer D Haendeler S Wester RA Pflug F Schroeder B Bagley JA Elling U Zuber J von Haeseler A Knoblich JA A human tissue screen identifies a regulator of ER secretion as a brain-size determinant Science 2020 370 935 + 10.1126/science.abb5390 33122427 · DOI · Paper page
- [48]Michels BE Mosa MH Streibl BI Zhan T Menche C Abou-El-Ardat K Darvishi T Czlonka E Wagner S Winter J Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids Cell Stem Cell 2020 26 782 792 e787 10.1016/j.stem.2020.04.003 32348727 · DOI · Paper page
- [50]Ringel T Frey N Ringnalda F Janjuha S Cherkaoui S Butz S Srivatsa S Pirkl M Russo G Villiger L Genome-Scale CRISPR Screening in Human Intestinal Organoids Identifies Drivers of TGF-beta Resistance Cell Stem Cell 2020 26 431 + 10.1016/j.stem.2020.02.007 32142663 · DOI · Paper page
- [51]Takeda H, Kataoka S, Nakayama M, Ali MAE, Oshima H, Yamamoto D, Park JW, Takegami Y, An T, Jenkins NA, et al. CRISPR-Cas9-mediated gene knockout in intestinal tumor organoids provides functional validation for colorectal cancer driver genes. Proc Natl Acad Sci U S A 2019. PMC6681705 31300537
- [52]Fleck JS, Jansen SMJ, Wollny D, Zenk F, Seimiya M, Jain A, Okamoto R, Santel M, He Z, Camp JG, Treutlein B. Inferring and perturbing cell fate regulomes in human brain organoids. Nature 2022. PMC10499607 36198796
- [53]Grigoriadis AE Wang ZQ Cecchini MG Hofstetter W Felix R Fleisch HA Wagner EF c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling Science 1994 266 443 448 10.1126/science.7939685 7939685 · DOI
- [54]Thomas DP Sunters A Gentry A Grigoriadis AE Inhibition of chondrocyte differentiation in vitro by constitutive and inducible overexpression of the c-fos proto-oncogene J Cell Sci 2000 113 Pt 3 439 450 10.1242/jcs.113.3.439 10639331 · DOI
- [55]Koo JH Plouffe SW Meng Z Lee DH Yang D Lim DS Wang CY Guan KL Induction of AP-1 by YAP/TAZ contributes to cell proliferation and organ growth Genes Dev 2020 34 72 86 10.1101/gad.331546.119 31831627 PMC6938666 · DOI
- [56]Saunders DN Hird SL Withington SL Dunwoodie SL Henderson MJ Biben C Sutherland RL Ormandy CJ Watts CK Edd, the murine hyperplastic disc gene, is essential for yolk sac vascularization and chorioallantoic fusion Mol Cell Biol 2004 24 7225 7234 10.1128/MCB.24.16.7225-7234.2004 15282321 PMC479729 · DOI
- [57]Swenson SA Gilbreath TJ Vahle H Hynes-Smith RW Graham JH Law HC Amador C Woods NT Green MR Buckley SM UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells Blood 2020 136 299 312 10.1182/blood.2019002102 32325489 PMC7365918 · DOI
- [58]Van de Sande B Flerin C Davie K De Waegeneer M Hulselmans G Aibar S Seurinck R Saelens W Cannoodt R Rouchon Q A scalable SCENIC workflow for single-cell gene regulatory network analysis Nat Protoc 2020 15 2247 2276 10.1038/s41596-020-0336-2 32561888 · DOI · Paper page
- [59]Jiang J Lyu P Li J Huang S Tao J Blackshaw S Qian J Wang J IReNA: Integrated regulatory network analysis of single-cell transcriptomes and chromatin accessibility profiles iScience 2022 25 105359 10.1016/j.isci.2022.105359 36325073 PMC9619378 · DOI
- [60]Trapnell C Cacchiarelli D Grimsby J Pokharel P Li S Morse M Lennon NJ Livak KJ Mikkelsen TS Rinn JL The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells Nat Biotechnol 2014 32 381 386 10.1038/nbt.2859 24658644 PMC4122333 · DOI · Paper page
Cited by
Sorted by citations
Lo, Y.-H., Horn, H. T., Huang, M.-F., Yu, W.-C., Young, C.-M., Liu, Q., Tomaske, M., Towers, M., Dominguez, A., Bassik, M. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62818-3 · Cited by 37 · see citing works
“Even more exciting is the implementation of CRISPR cutting screens in 3D organoids to explore factors such as growth factor dependency for cell growth 14 – 16 , identifying potential cancer-driving forces 17 – 19 , and uncovering key genetic events in cell differentiation 20 – 22 .”
- Authors
- Liang, J., Wei, J., Cao, J., Qian, J., Gao, R., Li, X., Wang, D., Gu, Y., Dong, L., Yu, J., Zhao, B., & Wang, X.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- State Key Laboratory of Pharmaceutical Biotechnology (CN)
- Nanchang University (CN)
- Corresponding author
- Zhao, Bing
- Wang, Xiaoyue
- ORCID
- Venue
- Genome Biology
- Published
- 2023-10-31
- Volume
- 24
- Issue
- 1
- Pages
- 251-251
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC10617096
- OpenAlex
- W4388069782
- Cited by
- 27
- References
- 18
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 2
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2018YFA0109800)
- National Natural Science Foundation of China (32122023, 32070603, 32022022, 31970761, 82172887)
- CAMS Innovation Fund for Medical Sciences (2021-I2M-1-066)
- National High Level Hospital Clinical Research Funding (2023-PUMCH-E-008)
- State Key Laboratory Special Fund (2060204)
- Key Research and Development Program of Yunnan Province (202302AA310024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- hepatocyte differentiation, hepatocyte maturation, liver organoids, transcription factor activity, FOS, UBR5
- MeSH terms
- Adult, Animals, Cell Differentiation, Humans, Liver, Organoids, Hepatocytes, Mice, Clustered Regularly Interspaced Short Palindromic Repeats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
