Space-time logic of liver gene expression at sub-lobular scale
Open accessPublished version of a preprint
Abstract
The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. However, liver zonation has previously been analysed as a static phenomenon, and liver chronobiology has been analysed at tissue-level resolution. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Using mixed-effect models of messenger RNA expression and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, and most of them show multiplicative space-time effects. Such dually regulated genes cover not only key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also previously unassociated processes involving protein chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our scRNA-seq analysis reveals how liver function is compartmentalized spatio-temporally at the sub-lobular scale.
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Gluconeogenesis-regulating genes are induced in periportal hepatocytes following prolonged starvation at the end of the resting phase.
“For example, gluconeogenesis-regulating genes are induced in periportal hepatocytes following prolonged starvation at the end of the resting phase.9,26”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [26]
The Results (Single-cell RNA-seq captures space-time gene expression patterns in mouse liver; page unavailable) report that Pck1, a gluconeogenesis-regulating gene, is expressed portally and peaks shortly before ZT12. Another Results passage describes mice as metabolically fasted near the end of the light phase. The copy supports the spatial and temporal pattern, but identifies one gene and does not establish induction following prolonged starvation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMorphogen expression, such as that of Wnt-family members, is shaped by hepatocyte zonation and can vary in time.
“Beyond metabolism, morphogen expression, such as that of Wnt-family members, is also shaped by this zonation and can vary in time7.”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [7]
The Results section reports that Wnt2 expression in pericentral non-parenchymal liver cells varies around the clock, supporting the temporal part of the claim. The Discussion describes Wnt ligands as forming a spatial gradient that contributes to zonated Wnt-target expression in hepatocytes; it does not show that hepatocyte zonation shapes morphogen expression. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSpatial gene expression in human hepatocytes is better described by a continuous variable determined by the relative distance between the portal and central areas of the lobule, similar to observations in mouse.
“Collectively, these observations suggest that spatial gene expression in human hepatocytes is better described by a continuous variable determined by the relative distance between the portal and central areas of the lobule, similar to observations in mouse7,26,27.”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [7]
The Results section describes spatial gene-expression profiles along the central–portal axis in mouse hepatocytes, supporting the comparison to mouse zonation. The study assigns cells to eight lobule layers using gene-expression landmarks; it does not establish that human hepatocyte expression is better described by a continuous variable determined by relative distance from the portal and central areas. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredClose to the inlet, where oxygen concentrations are highest, increased levels of the periportal marker proteins ARG1, BAAT, PYGL, FBP1 and ASL were observed.
“Close to the inlet, where oxygen concentrations are highest, we observed increased levels of the periportal marker proteins ARG1, BAAT, PYGL, FBP1 and ASL ( Fig. 6 a).”
From 3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation (2023) · cites this paper as [34]
The Results section (‘smFISH analysis of space-time mRNA counts’; page unavailable) reports portal-biased Arg1 mRNA, and ‘Space-time logic of hepatic functions’ says oxygen is most abundant portally. These passages do not establish increased protein levels for ARG1, BAAT, PYGL, FBP1 and ASL near the inlet; the reported Arg1 measurement is of mRNA, and the other four markers are not substantiated by the passages found. (LLM, conf=0.87)
Experimental — accuracy not yet measuredExpression of perivenous markers was significantly elevated close to the outlet where oxygenation is lower.
“In contrast, expression of perivenous markers was significantly elevated close to the outlet where oxygenation is lower.”
From 3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation (2023) · cites this paper as [34]
The Introduction (page unavailable) describes blood flowing from the portal side to the central vein, an accompanying oxygen gradient, and genes expressed more strongly near the central vein. The Discussion (page unavailable) also describes the central region as subject to hypoxic stress. These passages support the direction of the claim, but the cited text does not establish a statistically significant elevation of perivenous markers close to an outlet. (LLM, conf=0.81)
Experimental — accuracy not yet measured
The expression of WNT ligands is influenced by diurnal mRNA fluctuations, suggesting that WNT signalling may fluctuate throughout the day.
“Further, the expression of WNT ligands is influenced by diurnal mRNA fluctuations, suggesting that WNT signalling may fluctuate throughout the day.26”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [26]
Mutations in AGXT, predominantly expressed in periportal hepatocytes, result in primary hyperoxaluria type 1.
“For example, mutations in a single enzyme (AGXT), predominantly expressed in periportal hepatocytes, results in a life-threatening condition, primary hyperoxaluria type 1.26,156”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [26]
The Introduction (page unavailable) describes periportal gene-expression patterns generally, but does not identify AGXT. Searches for AGXT, alanine-glyoxylate aminotransferase, and primary hyperoxaluria found no passage in our copy addressing AGXT’s location or whether its mutations cause type 1 disease. (LLM, conf=0.74)
Experimental — accuracy not yet measuredAnimals fed ad libitum mapped to early zeitgeber timepoints, while samples for which food was removed the night before mapped to late zeitgeber timepoints.
“we confirmed that the animals that were fed ad libitum mapped to early zeitgeber timepoints, while samples for which food was removed the night before mapped to late zeitgeber timepoints”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [34]
The Results section reports ad libitum-fed mice sampled at ZT0, ZT6, ZT12 and ZT18; it does not report that ad libitum-fed samples mapped specifically to early timepoints. The Methods and Results passages found for overnight food removal and sample mapping do not describe food being removed the night before or those samples mapping to late timepoints. (LLM, conf=0.77)
Experimental — accuracy not yet measuredTo correct for batch effects, Harmony was used on the selected principal components.
“To correct for batch effects, we used Harmony on the selected principal components (34), using Leiden clustering with resolution 0.6, resulting in 15 clusters.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [34]
The Methods section on t-SNE clustering describes a low-dimensional representation, but does not mention Harmony or batch-effect correction. Searches for Harmony, batch correction, and selected principal components found no passage addressing the attributed method; page numbers are unavailable in our copy. (LLM, conf=0.73)
Experimental — accuracy not yet measured
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Cites
Estimating the Dimension of a Model
Schwarz, G. (1978) · The Annals of Statistics · doi:10.1214/aos/1176344136 · Cited by 47,033 · see citing works
(2008) · Journal of Machine Learning Research · Cited by 33,051 · see citing works
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-128 · Cited by 7,814 · see citing works
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055 · see citing works
Chapter 4 Preparation of Isolated Rat Liver Cells
Seglen, P. O. (1976) · Methods in cell biology · doi:10.1016/s0091-679x(08)61797-5 · Cited by 5,297 · see citing works
AIC model selection using Akaike weights
Wagenmakers, E.-J., & Farrell, S. (2004) · Psychonomic Bulletin & Review · doi:10.3758/bf03206482 · Cited by 2,684 · see citing works
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
A circadian gene expression atlas in mammals: Implications for biology and medicine
Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408886111 · Cited by 2,304 · see citing works
Jammalamadaka, S. R., & SenGupta, A. (2001) · Series on multivariate analysis · doi:10.1142/4031 · Cited by 1,824 · see citing works
Mop3 is an essential component of the master circadian pacemaker in mammals.
Bunger, M. K., Wilsbacher, L. D., Moran, S. M., Clendenin, C., Radcliffe, L. A., Hogenesch, J. B., Simon, M. C., Takahashi, J. S., & Bradfield, C. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00205-1 · Cited by 1,621 · see citing works
GARCÍA-ALONSO, C. R., Pérez, L. M., & Fernández, J. C. F. (2011) · Annals of Operations Research · doi:10.1007/s10479-011-0841-3 · Cited by 1,357 · see citing works
A human liver cell atlas reveals heterogeneity and epithelial progenitors
Aizarani, N., Saviano, A., Sagar, Mailly, L., Durand, S., Herman, J. S., Pessaux, P., Baumert, T. F., & Grün, D. (2019) · Nature · doi:10.1038/s41586-019-1373-2 · Cited by 1,147 · see citing works
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Halpern, K. B., Shenhav, R., Matcovitch-Natan, O., Tóth, B., Lemze, D., Golan, M., Massasa, E. E., Baydatch, S., Landen, S., Moor, A. E., et al. (2017) · Nature · doi:10.1038/nature21065 · Cited by 1,059 · see citing works
Self-citationGreen, C. B., Takahashi, J. S., & Bass, J. (2008) · Cell · doi:10.1016/j.cell.2008.08.022 · Cited by 902 · see citing works
Carmon, K. S., Gong, X. W., Lin, Q., Thomas, A., & Liu, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106083108 · Cited by 857 · see citing works
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Vollmers, C., Gill, S., DiTacchio, L., Pulivarthy, S. R., Le, H. D., & Panda, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909591106 · Cited by 765 · see citing works
ChIP‐Atlas: a data‐mining suite powered by full integration of public ChIP‐seq data
Oki, S., Ohta, T., Shioi, G., Hatanaka, H., Ogasawara, O., Okuda, Y., Kawaji, H., Nakaki, R., Sese, J., & Meno, C. (2018) · The EMBO Reports · doi:10.15252/embr.201846255 · Cited by 763 · see citing works
A QUANTITATIVE STEREOLOGICAL DESCRIPTION OF THE ULTRASTRUCTURE OF NORMAL RAT LIVER PARENCHYMAL CELLS
Loud, A. V. (1968) · The Journal of Cell Biology · doi:10.1083/jcb.37.1.27 · Cited by 727 · see citing works
Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion
Yu, L., Hammer, R. E., Li-Hawkins, J., von Bergmann, K., Lütjohann, D., Cohen, J. C., & Hobbs, H. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252582399 · Cited by 706 · see citing works
Classification of low quality cells from single-cell RNA-seq data
Ilicic, T., Kim, J. K., Kolodziejczyk, A. A., Bagger, F. O., McCarthy, D. J., Marioni, J. C., & Teichmann, S. A. (2016) · Genome Biology · doi:10.1186/s13059-016-0888-1 · Cited by 693 · see citing works
Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
Wang, B., Zhao, L., Fish, M., Logan, C. Y., & Nusse, R. (2015) · Nature · doi:10.1038/nature14863 · Cited by 674 · see citing works
Building and decoding ubiquitin chains for mitophagy
Harper, J. W., Ordureau, A., & Heo, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.129 · Cited by 668 · see citing works
Kornmann, B., Schaad, O., Bujard, H., Takahashi, J. S., & Schibler, U. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050034 · Cited by 658 · see citing works
Metabolic zonation of the liver: Regulation and implications for liver function
Gebhardt, R. (1992) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(92)90055-5 · Cited by 607 · see citing works
Individual recognition in mice mediated by major urinary proteins
Hurst, J. L., Payne, C. E., Nevison, C. M., Marie, A. D., Humphries, R. E., Robertson, D. H. L., Cavaggioni, A., & Beynon, R. J. (2001) · Nature · doi:10.1038/414631a · Cited by 605 · see citing works
A Unified Approach to Mixed Linear Models
McLean, R. A., Sanders, W. L., & Stroup, W. W. (1991) · The American Statistician · doi:10.1080/00031305.1991.10475767 · Cited by 602 · see citing works
Zonation of parenchymal and nonparenchymal metabolism in liver.
Jungermann, K., & Keitzmann, T. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001143 · Cited by 589 · see citing works
Circadian Rhythms and Metabolic Syndrome
Maury, E., Ramsey, K. M., & Bass, J. T. (2010) · Circulation Research · doi:10.1161/circresaha.109.208355 · Cited by 502 · see citing works
Metabolic zonation of the liver: The oxygen gradient revisited
Kietzmann, T. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.012 · Cited by 499 · see citing works
Spatial heterogeneity in the mammalian liver
Ben-Moshe, S., & Itzkovitz, S. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0134-x · Cited by 485 · see citing works
Self-citationREV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis
Martelot, G. L., Claudel, T., Gatfield, D., Schaad, O., Kornmann, B., Sasso, G. L., Moschetta, A., & Schibler, U. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000181 · Cited by 448 · see citing works
Ripperger, J. A., Shearman, L. P., Reppert, S. M., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.14.6.679 · Cited by 429 · see citing works
Robles, M. S., Cox, J., & Mann, M. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004047 · Cited by 383 · see citing works
Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells
Halpern, K. B., Shenhav, R., Massalha, H., Toth, B., Egozi, A., Massasa, E. E., Medgalia, C., David, E., Giladi, A., Moor, A. E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4231 · Cited by 368 · see citing works
Self-citationThe RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size
Planas-Paz, L., Orsini, V., Boulter, L., Calabrese, D., Pikiolek, M., Nigsch, F., Xie, Y., Roma, G., Donovan, A., Marti, P., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3337 · Cited by 359 · see citing works
Hoehme, S., Brulport, M., Bauer, A., Bedawy, E., Schormann, W., Hermes, M., Puppe, V., Gebhardt, R., Zellmer, S., Schwarz, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909374107 · Cited by 340 · see citing works
Model Selection in Linear Mixed Models
Müller, S., Scealy, J. L., & Welsh, A. H. (2013) · Statistical Science · doi:10.1214/12-sts410 · Cited by 330 · see citing works
Mauvoisin, D., Wang, J., Jouffe, C., Martin, E., Atger, F., Waridel, P., Quadroni, M., Gachon, F., & Naef, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314066111 · Cited by 329 · see citing works
Self-citationLiver zonation: Novel aspects of its regulation and its impact on homeostasis
Gebhardt, R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8491 · Cited by 275 · see citing works
Nitzan, M., Karaiskos, N., Friedman, N., & Rajewsky, N. (2019) · Nature · doi:10.1038/s41586-019-1773-3 · Cited by 272 · see citing works
Atger, F., Gobet, C., Marquis, J., Martín, E., Wang, J., Weger, B. D., Lefebvre, G. C., Descombes, P., Naef, F., & Gachon, F. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515308112 · Cited by 252 · see citing works
Self-citationTemporal orchestration of circadian autophagy rhythm by C/EBPβ
Ma, D., Panda, S., & Lin, J. D. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.322 · Cited by 234 · see citing works
Reinke, H., Saini, C., Fleury-Olela, F., Dibner, C., Benjamin, I. J., & Schibler, U. (2008) · Genes & Development · doi:10.1101/gad.453808 · Cited by 228 · see citing works
Dependence of Liver-Specific Transcription on Tissue Organization
Clayton, D. F., Harrelson, A. L., & Darnell, J. E., Jr. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2623 · Cited by 222 · see citing works
Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles
Sinturel, F., Gerber, A., Mauvoisin, D., Wang, J., Gatfield, D., Stubblefield, J. J., Green, C. B., Gachon, F., & Schibler, U. (2017) · Cell · doi:10.1016/j.cell.2017.04.015 · Cited by 222 · see citing works
Single-molecule mRNA detection and counting in mammalian tissue
Lyubimova, A., Itzkovitz, S., Junker, J. P., Fan, Z. P., Wu, X., & van Oudenaarden, A. (2013) · Nature Protocols · doi:10.1038/nprot.2013.109 · Cited by 206 · see citing works
Self-citationSpatial sorting enables comprehensive characterization of liver zonation
Ben-Moshe, S., Shapira, Y., Moor, A. E., Manco, R., Veg, T., Bahar Halpern, K., & Itzkovitz, S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0109-9 · Cited by 205 · see citing works
Self-citationSpatial sorting enables comprehensive characterization of liver zonation
Ben-Moshe, S., Shapira, Y., Moor, A. E., Halpern, K. B., & Itzkovitz, S. (2019) · doi:10.1101/529784 · Cited by 205 · see citing works
Self-citationMartelot, G. L., Canella, D., Symul, L., Migliavacca, E., Gilardi, F., Liechti, R., Martin, O., Harshman, K., Delorenzi, M., Desvergne, B., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001442 · Cited by 203 · see citing works
Self-citationT-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism in mice
Gougelet, A., Torre, C., Veber, P., Sartor, C., Bachelot, L., Denechaud, P.-D., Godard, C., Moldes, M., Burnol, A.-F., Dubuquoy, C., et al. (2014) · Hepatology · doi:10.1002/hep.26924 · Cited by 190 · see citing works
Nuclear Proteomics Uncovers Diurnal Regulatory Landscapes in Mouse Liver
Wang, J., Mauvoisin, D., Martín, E., Atger, F., Galindo, A. N., Dayon, L., Sizzano, F., Palini, A. G., Kussmann, M., Waridel, P., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.003 · Cited by 185 · see citing works
Self-citationDarnell, A. M., Subramaniam, A. R., & O’Shea, E. K. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.041 · Cited by 183 · see citing works
The hepatocyte clock and feeding control chronophysiology of multiple liver cell types
Guan, D., Xiong, Y., Trinh, T. M., Xiao, Y., Hu, W., Jiang, C., Dierickx, P., Jang, C., Rabinowitz, J. D., & Lazar, M. A. (2020) · Science · doi:10.1126/science.aba8984 · Cited by 173 · see citing works
Lavery, D. J., Lopez‐Molina, L., Margueron, R., Fleury-Olela, F., Conquet, F., Schibler, U., & Bonfils, C. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.6488 · Cited by 165 · see citing works
Circadian Dysregulation Disrupts Bile Acid Homeostasis
Ma, K., Xiao, R., Tseng, H.-T., Shan, L., Fu, L., & Moore, D. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006843 · Cited by 144 · see citing works
Kietzmann, T., Cornesse, Y., Brechtel-Curth, K., MODARESSI, S., & Jungermann, K. A. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3540531 · Cited by 141 · see citing works
Yeung, J., Mermet, J., Jouffe, C., Marquis, J., Charpagne, A., Gachon, F., & Naef, F. (2017) · Genome Research · doi:10.1101/gr.222430.117 · Cited by 107 · see citing works
Self-citationShort-Term Circadian Disruption Impairs Bile Acid and Lipid Homeostasis in Mice
Ferrell, J. M., & Chiang, J. Y. L. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.08.003 · Cited by 101 · see citing works
Clock-dependent chromatin topology modulates circadian transcription and behaviorPreprint
Mermet, J., Yeung, J., Hurni, C., Mauvoisin, D., Gustafson, K., Jouffe, C., Nicolas, D., Emmenegger, Y., Gobet, C., Franken, P., et al. (2018) · Genes & Development · doi:10.1101/gad.312397.118 · Cited by 101 · see citing works
Self-citationEpigenomic map of human liver reveals principles of zonated morphogenic and metabolic control
Brosch, M., Kattler, K., Herrmann, A., von Schönfels, W., Nordström, K., Seehofer, D., Damm, G., Becker, T., Zeissig, S., Nehring, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06611-5 · Cited by 98 · see citing works
Biochemical complexity drives log‐normal variation in genetic expression
Beal, J. (2017) · Engineering Biology · doi:10.1049/enb.2017.0004 · Cited by 95 · see citing works
Transcriptional regulatory logic of the diurnal cycle in the mouse liver
Sobel, J., Krier, I., Andersin, T., Raghav, S. K., Canella, D., Gilardi, F., Kalantzi, A., Rey, G., Weger, B. D., Gachon, F., et al. (2017) · PLoS Biology · doi:10.1371/journal.pbio.2001069 · Cited by 91 · see citing works
Self-citationTemperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene CirbpPreprint
Gotić, I., Omidi, S., Fleury-Olela, F., Molina, N., Naef, F., & Schibler, U. (2016) · Genes & Development · doi:10.1101/gad.287094.116 · Cited by 87 · see citing works
Self-citationWang, J., Symul, L., Yeung, J., Gobet, C., Sobel, J., Lück, S., Westermark, P. O., Molina, N., & Naef, F. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715225115 · Cited by 67 · see citing works
Self-citationThe Wnt/β-catenin pathway: master regulator of liver zonation?
Burke, Z. D., & Tosh, D. (2006) · BioEssays · doi:10.1002/bies.20485 · Cited by 66 · see citing works
Kuhn, N. J., Woodworth-Gutai, M., Gross, K. W., & Held, W. A. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.15.6073 · Cited by 64 · see citing works
Jakobsson, A., Jörgensen, J. A., & Jacobsson, A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00045.2005 · Cited by 61 · see citing works
Yeung, J., & Naef, F. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.09.005 · Cited by 58 · see citing works
Self-citationColnot, S., & Perret, C. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-7107-4_2 · Cited by 50 · see citing works
Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic WorldPreprint
Mermet, J., Yeung, J., & Naef, F. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028720 · Cited by 42 · see citing works
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The immunological and metabolic landscape in primary and metastatic liver cancer
Li, X., Ramadori, P., Pfister, D., Seehawer, M., Zender, L., & Heikenwalder, M. (2021) · Nature Reviews. Cancer · doi:10.1038/s41568-021-00383-9 · Cited by 580 · see citing works
DestVI identifies continuums of cell types in spatial transcriptomics data
Lopez, R., Li, B., Keren-Shaul, H., Boyeau, P., Kedmi, M., Pilzer, D., Jelinski, A., Yofe, I., David, E., Wagner, A., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01272-8 · Cited by 276 · see citing works
“Turning to hepatocytes, we used DestVI to explore how hepatocyte-specific gene expression pertains to liver zonation [77].”
MethodThe spatiotemporal program of zonal liver regeneration following acute injury
Ben-Moshe, S., Veg, T., Manco, R., Dan, S., Papinutti, D., Lifshitz, A., Kolodziejczyk, A. A., Bahar Halpern, K., Elinav, E., & Itzkovitz, S. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.008 · Cited by 224 · see citing works
Self-citationSpatial single-cell mass spectrometry defines zonation of the hepatocyte proteome
Rosenberger, F. A., Thielert, M., Strauss, M. T., Schweizer, L., Ammar, C., Mädler, S. C., Metousis, A., Skowronek, P., Wahle, M., Madden, K., et al. (2023) · Nature Methods · doi:10.1038/s41592-023-02007-6 · Cited by 176 · see citing works
Amino acid metabolism, transport and signalling in the liver revisited.
Paulusma, C., Lamers, W., Bröer, S., & van de Graaf, S. V. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115074 · Cited by 162 · see citing works
Paris, J., & Henderson, N. C. (2022) · Hepatology · doi:10.1002/hep.32408 · Cited by 167 · see citing works
Liver Zonation – Revisiting Old Questions With New Technologies
Cunningham, R. P., & Porat‐Shliom, N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.732929 · Cited by 166 · see citing works
Interconnections between circadian clocks and metabolism
Guan, D., & Lazar, M. A. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148278 · Cited by 166 · see citing works
Berthier, A., Johanns, M., Zummo, F. P., Lefebvre, P., & Staels, B. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166097 · Cited by 125 · see citing works
Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution
Watson, B. R., Paul, B., Rahman, R. U., Amir-Zilberstein, L., Segerstolpe, Å., Epstein, E. T., Murphy, S., Geistlinger, L., Lee, T., Shih, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55325-4 · Cited by 123 · see citing works
Cheng, M. L., Nakib, D., Perciani, C. T., & MacParland, S. A. (2021) · Clinical Science · doi:10.1042/cs20190654 · Cited by 122 · see citing works
Spatiotemporal Metabolic Liver Zonation and Consequences on Pathophysiology
Martini, T., Naef, F., & Tchorz, J. S. (2023) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-024831 · Cited by 113 · see citing works
Self-citationSpatial metabolomics and its application in the liver
Santos, A. A., Delgado, T. C., Marques, V., Ramírez-Moncayo, C., Alonso, C., Vidal‐Puig, A., Hall, Z., Martínez‐Chantar, M. L., & Rodrigues, C. M. P. (2023) · Hepatology · doi:10.1097/hep.0000000000000341 · Cited by 100 · see citing works
Bravo González-Blas, C., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-023-01316-4 · Cited by 85 · see citing works
“To obtain the circadian rhythm signatures, we used the scRNA-seq data from the mouse liver at different timepoints of the circadian rhythm from a previous study 81 , performing differential expression analysis between the different timepoints with Seurat (v.4.0.03) 71 .”
InfluentialDisentanglement of single-cell data with biolord
Piran, Z., Cohen, N., Hoshen, Y., & Nitzan, M. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02079-x · Cited by 84 · see citing works
Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine
Cangelosi, A. L., Puszynska, A. M., Roberts, J. M., Armani, A., Nguyen, T. P., Spinelli, J., Kunchok, T., Wang, B., Chan, S. H., Lewis, C. A., et al. (2022) · Science · doi:10.1126/science.abi9547 · Cited by 64 · see citing works
A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage
Afriat, A., Zuzarte‐Luís, V., Halpern, K. B., Buchauer, L., Marques, S., Chora, Â. F., Lahree, A., Amit, I., Mota, M. M., & Itzkovitz, S. (2022) · Nature · doi:10.1038/s41586-022-05406-5 · Cited by 61 · see citing works
Self-citationKang, S. W. S., Cunningham, R. P., Miller, C. B., Brown, L. A., Cultraro, C. M., Harned, A., Narayan, K., Hernandez, J. M., Jenkins, L. M. M., Lobanov, A. V., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45751-9 · Cited by 61 · see citing works
Locally sourced: site-specific immune barriers to metastasis
Correia, A. L. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00836-2 · Cited by 58 · see citing works
Priming and Maintenance of Adaptive Immunity in the Liver
Kawashima, K., Andreata, F., Beccaría, C. G., & Iannacone, M. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090122-041354 · Cited by 55 · see citing works
Circadian and Sleep Metabolomics Across Species
Malik, D. M., Paschos, G. K., Sehgal, A., & Weljie, A. M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.04.027 · Cited by 52 · see citing works
Hu, K., Kuhn, N. F., Courau, T., Tsui, J. L., Samad, B., Ha, P. K., Kratz, J., Combes, A., & Krummel, M. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.05.001 · Cited by 45 · see citing works
Single-cell and spatially resolved transcriptomics for liver biology
Lin, P., Yan, X., Jing, S., Wu, Y., Shan, Y., Guo, W., Gu, J., Li, Y., Zhang, H., & Li, H. (2023) · Hepatology · doi:10.1097/hep.0000000000000387 · Cited by 53 · see citing works
Christ, B., Collatz, M., Dahmen, U., Herrmann, K., Höpfl, S., König, M., Lambers, L., Marz, M., Meyer, D., Radde, N. E., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.733868 · Cited by 46 · see citing works
Circadian Regulation of Gene Expression and Metabolism in the Liver
Guan, D., & Lazar, M. A. (2022) · Seminars in Liver Disease · doi:10.1055/a-1792-4240 · Cited by 47 · see citing works
Goldfarb, C. N., Karri, K., Pyatkov, M., & Waxman, D. J. (2022) · Endocrinology · doi:10.1210/endocr/bqac059 · Cited by 46 · see citing works
The RSPO‐LGR4/5‐ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease
Annunziato, S., Sun, T., & Tchorz, J. S. (2022) · Hepatology · doi:10.1002/hep.32328 · Cited by 45 · see citing works
Trinh, V. Q.-H., Lee, T.-F., Lemoinne, S., Ray, K. C., Ybanez, M. D., Tsuchida, T., Carter, J. K., Agudo, J., Brown, B. D., Akat, K. M., et al. (2023) · Science Signaling · doi:10.1126/scisignal.adf6696 · Cited by 45 · see citing works
The hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression
Fougeray, T., Polizzi, A., Régnier, M., Fougerat, A., Ellero‐Simatos, S., Lippi, Y., Smati, S., Lasserre, F., Tramunt, B., Huillet, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110674 · Cited by 40 · see citing works
Wesseler, M. F., Taebnia, N., Harrison, S., Youhanna, S., Preiss, L. C., Kemas, A. M., Vegvari, A., Mokry, J., Sullivan, G. J., Lauschke, V. M., et al. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.09.022 · Cited by 39 · see citing works
Cannabinoid receptor 1 signaling in hepatocytes and stellate cells does not contribute to NAFLD
Wang, S., Zhu, Q., Liang, G., Franks, T., Boucher, M., Bence, K. K., Lu, M., Castorena, C. M., Zhao, S., Elmquist, J. K., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci152242 · Cited by 37 · see citing works
Recent advances in liver‐on‐chips: Design, fabrication, and applications
Qiu, L., Kong, B., Kong, T., & Wang, H. (2023) · Smart Medicine · doi:10.1002/smmd.20220010 · Cited by 37 · see citing works
Distinct hepatocyte identities in liver homeostasis and regeneration
Chen, F., Schönberger, K., & Tchorz, J. S. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100779 · Cited by 30 · see citing works
Circadian regulation of digestive and metabolic tissues
Taleb, Z., & Karpowicz, P. A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00166.2022 · Cited by 30 · see citing works
Hepatocyte SREBP signaling mediates clock communication within the liver
Guan, D., Bae, H., Zhou, D., Chen, Y., Jiang, C., La, C. M., Xiao, Y., Zhu, K., Hu, W., Trinh, T. M., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci163018 · Cited by 29 · see citing works
Spatial transcriptome profiling of normal human liver
Yu, S., Wang, H., Yang, L., Yan, Y., Cai, Q., Ma, D., Jiang, L., Gao, Z., Yu, Z., & Xia, Z. (2022) · Scientific Data · doi:10.1038/s41597-022-01676-w · Cited by 28 · see citing works
Kang, S. W. S., Brown, L. A., Miller, C. B., Barrows, K. M., Golino, J. L., Liu, H., Cultraro, C. M., Feliciano, D., Cornelius-Muwanuzi, M. B., Remmert, K., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01476-1 · Cited by 28 · see citing works
Hildebrandt, F., Iturritza, M. U., Zwicker, C., Vanneste, B., Hul, N. V., Semle, E., Quin, J. E., Pascini, T. V., Saarenpää, S., He, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51418-2 · Cited by 25 · see citing works
Auerbach, B. J., FitzGerald, G. A., & Li, M. (2022) · Nature Communications · doi:10.1038/s41467-022-34185-w · Cited by 25 · see citing works
Perturbed liver gene zonation in a mouse model of non-alcoholic steatohepatitis
Zhou, Y., Zhao, Y., Carbonaro, M., Chen, H., Germino, M., Adler, C., Ni, M., Zhu, Y. O., Kim, S. Y., Altarejos, J., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155830 · Cited by 24 · see citing works
Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling
He, B., Copps, K. D., Stöhr, O., Liu, B., Hu, S., Joshi, S., Haigis, M. C., White, M. F., Zhu, H., & Tao, R. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.03.015 · Cited by 25 · see citing works
Escalante‐Covarrubias, Q., Mendoza-Viveros, L., González-Suárez, M., Sitten-Olea, R., Velázquez‐Villegas, L. A., Becerril-Pérez, F., Pacheco-Bernal, I., Carreño‐Vázquez, E., Sanchez, P. B. M., Bustamante-Zepeda, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37286-2 · Cited by 24 · see citing works
Circadian rhythms and the liver
Costa, R., Mangini, C., Domenie, E. D., Zarantonello, L., & Montagnese, S. (2023) · Liver International · doi:10.1111/liv.15501 · Cited by 23 · see citing works
A spatial atlas of the healthy human liver from live donors
Yakubovsky, O., Halpern, K. B., Shir, S., Novoselsky, R., Afriat, A., Egozi, A., Barkai, T., Harnik, Y., Hoefflin, R., Kohanim, Y. K., et al. (2026) · Nature · doi:10.1038/s41586-026-10377-y · Cited by 23 · see citing works
Self-citationRoles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis
Ma, L., Li, C., & Wang, X. W. (2025) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-111523-023520 · Cited by 19 · see citing works
Abu‐Elala, N. M., Khattab, M. S., AbuBakr, H. O., Helmy, S., Hesham, A., Younis, N. A., Dawood, M. A. O., & Basuini, M. F. E. (2023) · Scientific Reports · doi:10.1038/s41598-023-36121-4 · Cited by 20 · see citing works
Dai, W., Wang, Z., Wang, G., Wang, Q. A., DeBerardinis, R. J., & Jiang, L. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112971 · Cited by 19 · see citing works
Chronic sleep deprivation impairs retinal circadian transcriptome and visual function
Huang, S., Zhang, W., Xuan, S., Si, H., Huang, D., Ba, M., Qi, D., Pei, X., Lu, D., & Li, Z. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.109907 · Cited by 20 · see citing works
Karin, J., Bornfeld, Y., & Nitzan, M. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01663-5 · Cited by 18 · see citing works
Zonation, Zonation, Zonation: The Real Estate of the Liver
Yasaka, T. M., Kim, C., Meadows, V., & Monga, S. P. (2025) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-042624-091820 · Cited by 21 · see citing works
SiFT: uncovering hidden biological processes by probabilistic filtering of single-cell data
Piran, Z., & Nitzan, M. (2024) · Nature Communications · doi:10.1038/s41467-024-44757-7 · Cited by 16 · see citing works
Okada, J., Landgraf, A., Xiaoli, A. M., Liu, L. P., Horton, M., Schuster, V. L., Yang, F., Sidoli, S., Qiu, Y., Kurland, I. J., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01269-y · Cited by 16 · see citing works
Compartmentalization, cooperation, and communication: The 3Cs of Hepatocyte zonation
Porat‐Shliom, N. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102292 · Cited by 16 · see citing works
Lineage motifs as developmental modules for control of cell type proportions
Tran, M., Askary, A., & Elowitz, M. B. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.01.017 · Cited by 16 · see citing works
Hansen, D., Jensen, J. E. R., Andersen, C. A. T., Jakobsgaard, P. R., Havelund, J. F., Lauritsen, L., Mandacaru, S. C., Siersbæk, M. S., Shackleton, O. L., Inoue, H., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.01.022 · Cited by 16 · see citing works
Stopka, S. A., Stopka, S. A., Abdelmoula, W. M., Ruiz, D. F., Joshi, S., Ringel, A. E., Haigis, M. C., & Agar, N. Y. R. (2022) · PLoS ONE · doi:10.1371/journal.pone.0261803 · Cited by 16 · see citing works
Hepatic Zonation in MASLD: Old Question, New Challenge in the Era of Spatial Omics
Paolini, E., Longo, M., Meroni, M., & Dongiovanni, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110701 · Cited by 16 · see citing works
A time- and space-resolved nuclear receptor atlas in mouse liver
Zummo, F. P., Berthier, A., Gheeraert, C., Vinod, M., Bobowski, M., Molendi‐Coste, O., Pineau, L., Jung, M., Guille, L., Dubois‐Chevalier, J., et al. (2023) · Journal of Molecular Endocrinology · doi:10.1530/jme-23-0017 · Cited by 15 · see citing works
Liver in infections: a single-cell and spatial transcriptomics perspective
Zou, J., Li, J., Zhong, X. Y., Tang, D., Fan, X., & Chen, R. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00945-z · Cited by 16 · see citing works
McCommis, K. S., & Finck, B. N. (2023) · Biomolecules · doi:10.3390/biom13020261 · Cited by 14 · see citing works
Martini, T., Gobet, C., Salati, A., Blanc, J., Mookhoek, A., Reinehr, M. D., Knott, G. W., Sordet‐Dessimoz, J., & Naef, F. (2024) · Nature Communications · doi:10.1038/s41467-024-52751-2 · Cited by 13 · see citing works
Self-citationMessner, C. J., Babrak, L. M., Titolo, G., Caj, M., Miho, E., & Suter‐Dick, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094372 · Cited by 13 · see citing works
Hepatic Positron Emission Tomography: Applications in Metabolism, Haemodynamics and Cancer
Honka, M., Rebelos, E., Malaspina, S., & Nuutila, P. (2022) · Metabolites · doi:10.3390/metabo12040321 · Cited by 13 · see citing works
Poole, J., & Ray, D. W. (2022) · Journal of Biological Rhythms · doi:10.1177/07487304221092727 · Cited by 13 · see citing works
Spatial gene regulatory networks driving cell state transitions during human liver disease
Hammond, N. L., Baker, S. M., Georgaka, S., Al-Anbaki, A., Jokl, E. J., Simpson, K., Sánchez‐Alvarez, R., Athwal, V. S., Purssell, H., Siriwardena, A. K., et al. (2025) · EMBO Molecular Medicine · doi:10.1038/s44321-025-00230-6 · Cited by 15 · see citing works
Significance of Liver Zonation in Hepatocellular Carcinoma
Yu, S., Gao, J., Wang, H., Liu, L., Liu, X., Xu, Y., Shi, J., Guo, W., & Zhang, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.806408 · Cited by 12 · see citing works
Unraveling the Complexity of Liver Disease One Cell at a Time
Bader, G. D., McGilvray, I. D., MacParland, S. A., Atif, J., & Thoeni, C. E. (2022) · Seminars in Liver Disease · doi:10.1055/s-0042-1755272 · Cited by 12 · see citing works
Liver regeneration: unraveling the molecular mechanisms and clinical application
Wang, N., Guo, M., Zhang, C., Jiang, R., Bi, J., Sun, J., & Liu, B. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07412-3 · Cited by 14 · see citing works
Gatlin, V., Gupta, S., Romero, S., Chapkin, R. S., & Cai, J. J. (2025) · npj Systems Biology and Applications · doi:10.1038/s41540-025-00507-z · Cited by 12 · see citing works
Intracellular spatiotemporal metabolism in connection to target engagement
Zhang, J., Qiu, Z., Zhang, Y. J., Wang, G., & Hao, H. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115024 · Cited by 10 · see citing works
Getting in the zone: Metabolite transport across liver zones
van de Graaf, S. V. D., Paulusma, C., & Panhuis, W. I. H. (2024) · Acta Physiologica · doi:10.1111/apha.14239 · Cited by 11 · see citing works
Habashy, A., Acree, C., Keun-young Kim, A., Zahraei, A., Dufresne, M., Phan, S., Cutler, M., Patterson, E., Mulligan, A. G., Burkewitz, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60994-w · Cited by 9 · see citing works
Zonated quantification of immunohistochemistry in normal and steatotic livers
Peleman, C., Vos, W. D. D., Pintelon, I., Driessen, A., van Eyck, A., Steenkiste, C. V., Vonghia, L., Man, J. G. D., Winter, B. D., Berghe, T. V., et al. (2023) · Virchows Archiv · doi:10.1007/s00428-023-03496-8 · Cited by 9 · see citing works
Emerging Roles of Spatial Transcriptomics in Liver Research
Fujiwara, N., Kimura, G., & Nakagawa, H. (2024) · Seminars in Liver Disease · doi:10.1055/a-2299-7880 · Cited by 11 · see citing works
Sonkar, R., Ma, H., & Waxman, D. J. (2024) · Toxicological Sciences · doi:10.1093/toxsci/kfae057 · Cited by 7 · see citing works
Blocking H1R signal aggravates atherosclerosis by promoting inflammation and foam cell formation
Zhu, B., Yang, Y., Wang, X., Sun, D., Yang, X., Zhu, X., Ding, S., Xiao, C., Zou, Y., & Yang, X. (2024) · Journal of Molecular Medicine · doi:10.1007/s00109-024-02453-5 · Cited by 8 · see citing works
Liver zonation—a journey through space and time
Annunziato, S., & Tchorz, J. S. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00333-z · Cited by 8 · see citing works
Liver as a nexus of daily metabolic cross talk
Litwin, C., & Koronowski, K. B. (2024) · International review of cytology · doi:10.1016/bs.ircmb.2024.06.001 · Cited by 8 · see citing works
NicheTrans: spatial-aware cross-omics translation
Wang, Z., Zou, Q., Lin, S., Li, S., Cui, Y., Zhang, D., Han, C., Li, Y., Li, J., Zhao, Y. C., et al. (2026) · Nature Methods · doi:10.1038/s41592-026-03153-3 · Cited by 9 · see citing works
Wang, X., Si, Q., Yang, N., Li, Y., Tang, L., Li, J., Zeng, H., Li, T., Chen, S., & Guo, T. (2025) · Regenerative Biomaterials · doi:10.1093/rb/rbaf061 · Cited by 7 · see citing works
Ming, Z., Luo, T., Zou, Z., Luo, W., Hu, X., Chen, L., Zhou, J., Liu, X., Mingquan, L., Li, J., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000769 · Cited by 7 · see citing works
Landgraf, A., Okada, J., Horton, M., Liu, L. P., Solomon, S., Qiu, Y., Kurland, I. J., Sidoli, S., Pessin, J. E., & Shinoda, K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.15.649020 · Cited by 7 · see citing works
Profiling metabolome of mouse embryonic cerebrospinal fluid following maternal immune activation
Petrova, B., Lacey, T. E., Culhane, A. J., Cui, J., Brook, J. R., Raskind, A. B., Misra, A., Lehtinen, M. K., & Kanarek, N. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107749 · Cited by 9 · see citing works
Rspo3-mediated metabolic liver zonation regulates systemic glucose metabolism and body mass in mice
Uno, K., Uchino, T., SUZUKI, T. A., 遥平, 佐., Edo, N., uno, K., Morita, K., Ishikawa, T., Koizumi, M., Honda, H., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3002955 · Cited by 6 · see citing works
Enhancer grammar of liver cell types and hepatocyte zonation states
González-Blas, C. B., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2022) · doi:10.1101/2022.12.08.519575 · Cited by 5 · see citing works
Wang, S., Xu, B., Liang, J., Feng, Y., Han, P., Shen, J., Li, X., Zheng, M., Zhang, T., Zhang, C., et al. (2024) · Advanced Science · doi:10.1002/advs.202405240 · Cited by 5 · see citing works
Sen, A., Youssef, S., Wendt, K., & Anakk, S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105322 · Cited by 5 · see citing works
Hur, S., Jeong, H., Kim, K., Kim, K. H., Kim, S. H., Lee, Y., & Nam, K. T. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07217-0 · Cited by 5 · see citing works
Nikhat, A., Mandal, T., Veerasubramanian, N., & Chakrabarti, S. (2026) · iScience · doi:10.1016/j.isci.2026.115394 · Cited by 4 · see citing works
Two types of regenerative cell populations appear in acute liver injury
Aoyagi, T., Goya, T., Imoto, K., Azuma, Y., Hioki, T., Kohjima, M., Tanaka, M., Oda, Y., & Ogawa, Y. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102503 · Cited by 4 · see citing works
Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle
Zhu, B. (2022) · Physiology · doi:10.1152/physiol.00003.2022 · Cited by 4 · see citing works
Precise cell therapy for liver fibrosis: Endothelial cell and macrophage therapy
Deng, L., Wu, B., Liang, K., Liao, H., & Du, Y. (2022) · iLIVER · doi:10.1016/j.iliver.2022.11.002 · Cited by 4 · see citing works
The spatio-temporal program of liver zonal regenerationPreprint
Ben‐Moshe, S., Veg, T., Manco, R., Dan, S., Kolodziejczyk, A. A., Halpern, K. B., Elinav, E., & Itzkovitz, S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.11.455924 · Cited by 4 · see citing works
Self-citationBiological representation disentanglement of single-cell dataPreprint
Piran, Z., Cohen, N., Hoshen, Y., & Nitzan, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.05.531195 · Cited by 4 · see citing works
Spatial Transcriptomics Sequencing of Mouse Liver at 2µm Resolution Using a Novel Spatial DNA ChipPreprint
Ding, X., Hoff, K., Swaminathan, R., Koutrouli, M., Pollom, S., Huang, T., Li, X., Zhou, G., Bai, Z., Yu, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.08.574734 · Cited by 4 · see citing works
Single-Cell Multiomic Analysis of Circadian Rhythmicity in Mouse LiverPreprint
Tong, C.-Y., Li, C., Jacq, A., Nie, X. Y., Guy, C. R., Suh, J. H., Wong, R. K. W., Merlin, C., Menet, J. S., & Jiang, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.03.647044 · Cited by 4 · see citing works
Spatial Single‐Cell Technologies for Exploring Gastrointestinal Tissue Transcriptome
Kang, H. M., & Lee, J. H. (2023) · Comprehensive physiology · doi:10.1002/j.2040-4603.2023.tb00266.x · Cited by 3 · see citing works
Martinez, M. A., Combriat, T. M. D., Ferencevic, K., Wilhelmsen, I., Dalmao‐Fernández, A., Olsen, P. A., Stokowiec, J., Aizenshtadt, A., & Krauss, S. J. K. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1528991 · Cited by 3 · see citing works
Scheidecker, B., Poulain, S., Sugimoto, M., Arakawa, H., Kim, S. H., Kawanishi, T., Kato, Y., Danoy, M., Nishikawa, M., & Sakai, Y. (2024) · Biotechnology and Bioengineering · doi:10.1002/bit.28653 · Cited by 3 · see citing works
Chen, S., Regev, A., Condon, A., & Ding, J. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.101073 · Cited by 3 · see citing works
- Authors
- Droin, C., Kholtei, J. E., Bahar Halpern, K., Hurni, C., Rozenberg, M., Muvkadi, S., Itzkovitz, S., & Naef, F.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Weizmann Institute of Science (IL)
- Corresponding author
- Itzkovitz, Shalev
- Venue
- Nature Metabolism
- Published
- 2021-01-11
- Volume
- 3
- Issue
- 1
- Pages
- 43-58
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC7116850
- OpenAlex
- W3119677722
- Cited by
- 148
- References
- 71
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 27 · 2023: 31 · 2022: 26 · 2021: 13 · 2020: 1
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_173079)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- liver zonation, circadian clock, gene expression rhythms, hepatocyte heterogeneity, Wnt signaling, central vein, non-parenchymal cells, molecular chaperones, lipid metabolism, carbohydrate metabolism, amino acid metabolism
- MeSH terms
- Algorithms, Amino Acids, Animals, Liver, Male, Mice, Inbred C57BL, Periodicity, RNA, Messenger, Gene Expression, Molecular Chaperones, Gene Expression Profiling, Hepatocytes, Carbohydrate Metabolism, Lipid Metabolism, Mice, Period Circadian Proteins, Circadian Clocks, Wnt Signaling Pathway
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