Ben-Moshe, S. et al. The spatiotemporal program of zonal liver regeneration following acute injury. Cell Stem Cell 29, 973–989.e10 (2022). This article describes the use of spatially resolved single-cell RNA-seq to profile regeneration following drug-induced acute pericentral damage, and shows a transient upregulation of oncofetal genes while hepatocytes proliferate and are zonally reprogrammed to replace necrotic pericentral hepatocytes.

Article  CAS  PubMed  Google Scholar 

Font-Burgada, J. et al. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162, 766–779 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tarlow, B. D. et al. Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 15, 605–618 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deng, X. et al. Chronic liver injury induces conversion of biliary epithelial cells into hepatocytes. Cell Stem Cell 23, 114–122.e3 (2018).

Article  CAS  PubMed  Google Scholar 

Cheemerla, S. & Balakrishnan, M. Global epidemiology of chronic liver disease. Clin. Liver Dis. 17, 365–370 (2021).

Article  Google Scholar 

Tremblay, K. D. & Zaret, K. S. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev. Biol. 280, 87–99 (2005).

Article  CAS  PubMed  Google Scholar 

Wang, J., Rhee, S., Palaria, A. & Tremblay, K. D. FGF signaling is required for anterior but not posterior specification of the murine liver bud. Dev. Dyn. 244, 431–443 (2015).

Article  CAS  PubMed  Google Scholar 

Palaria, A., Angelo, J. R., Guertin, T. M., Mager, J. & Tremblay, K. D. Patterning of the hepato‐pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud. Hepatology 68, 274–288 (2018).

Article  CAS  PubMed  Google Scholar 

Houssaint, E. Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. Cell Differ. 9, 269–279 (1980).

Article  CAS  PubMed  Google Scholar 

Gualdi, R. et al. Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev. 10, 1670–1682 (1996).

Article  CAS  PubMed  Google Scholar 

Jung, J., Zheng, M., Goldfarb, M. & Zaret, K. S. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 284, 1998–2003 (1999).

Article  CAS  PubMed  Google Scholar 

Bort, R., Signore, M., Tremblay, K., Barbera, J. P. M. & Zaret, K. S. Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev. Biol. 290, 44–56 (2006).

Article  CAS  PubMed  Google Scholar 

Margagliotti, S. et al. Role of metalloproteinases at the onset of liver development. Dev. Growth Differ. 50, 331–338 (2008).

Article  CAS  PubMed  Google Scholar 

Alder, O. et al. Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell Rep. 9, 261–271 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iwafuchi-Doi, M. et al. The pioneer transcription factor FoxA maintains an accessible nucleosome configuration at enhancers for tissue-specific gene activation. Mol. Cell 62, 79–91 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gordillo, M., Evans, T. & Gouon-Evans, V. Orchestrating liver development. Development 142, 2094–2108 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hikspoors, J. P. J. M. et al. The fate of the vitelline and umbilical veins during the development of the human liver. J. Anat. 231, 718–735 (2017). This article describes a comprehensive examination of the fate of mouse, pig and human vitelline and umbilical vein during hepatogenesis.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lotto, J. et al. Single-cell transcriptomics reveals early emergence of liver parenchymal and non-parenchymal cell lineages. Cell 183, 702–716.e14 (2020). This article describes a comprehensive single-cell atlas of hepatic cell development, detailing diversity and differentiation of parenchymal and non-parenchymal cell types, including a distinct hepatic cell type displaying a hybrid hepatic–mesenchymal phenotype.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, H. et al. Genetic lineage tracing identifies endocardial origin of liver vasculature. Nat. Genet. 48, 537–543 (2016). Using intersectional genetics and lineage tracing, this article shows that a considerable number of liver endothelial cells originate from the dorsal aspect of the endocardium in mice.

Article  PubMed  Google Scholar 

Lee, L. K. et al. LYVE1 marks the divergence of yolk sac definitive hemogenic endothelium from the primitive erythroid lineage. Cell Rep. 17, 2286–2298 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Swartley, O. M., Foley, J. F., Livingston, D. P., Cullen, J. M. & Elmore, S. A. Histology atlas of the developing mouse hepatobiliary hemolymphatic vascular system with emphasis on embryonic days 11.5–18.5 and early postnatal development. Toxicol. Pathol. 44, 705–725 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sugiyama, Y. et al. Sinusoid development and morphogenesis may be stimulated by VEGF‐Flk‐1 signaling during fetal mouse liver development. Dev. Dyn. 239, 386–397 (2010).

Article  CAS  PubMed  Google Scholar 

DeSesso, J. M. Vascular ontogeny within selected thoracoabdominal organs and the limbs. Reprod. Toxicol. 70, 3–20 (2017).

Article  CAS  PubMed  Google Scholar 

Lassau, J. P. & Bastian, D. Organogenesis of the venous structures of the human liver: a hemodynamic theory. Anat. Clin. 5, 97–102 (1983).

Article  Google Scholar 

Ema, H. & Nakauchi, H. Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95, 2284–2288 (2000).

Article  CAS  PubMed  Google Scholar 

Johnson, G. R. & Moore, M. A. S. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis. Nature 258, 726–728 (1975).

Article  CAS  PubMed  Google Scholar 

Zovein, A. C. et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3, 625–636 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Medvinsky, A. & Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897–906 (1996).

Article  CAS  PubMed  Google Scholar 

Hirsch, E., Iglesias, A., Potocnik, A. J., Hartmann, U. & Fässler, R. Impaired migration but not differentiation of haematopoietic stem cells in the absence of β1 integrins. Nature 380, 171–175 (1996).

Article  CAS  PubMed  Google Scholar 

Emambokus, N. R. & Frampton, J. The glycoprotein IIb molecule is expressed on early murine hematopoietic progenitors and regulates their numbers in sites of hematopoiesis. Immunity 19, 33–45 (2003).

Article  CAS  PubMed  Google Scholar 

Ara, T. et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 19, 257–267 (2003).

Article  CAS  PubMed  Google Scholar 

Ding, L., Saunders, T. L., Enikolopov, G. & Morrison, S. J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457–462 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Khan, J. A. et al. Fetal liver hematopoietic stem cell niches associate with portal vessels. Science 351, 176–180 (2016).

Article  CAS  PubMed  Google Scholar 

Ceredig, R., Rolink, A. G. & Brown, G. Models of haematopoiesis: seeing the wood for the trees. Nat. Rev. Immunol. 9, 293–300 (2009).

Article  CAS  PubMed  Google Scholar 

Lorenz, L. et al. Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival. Nature 562, 128–132 (2018).

Article  CAS  PubMed  Google Scholar 

Antoniou, A. et al. Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology 136, 2325–2333 (2009).

Article  PubMed  Google Scholar 

Zong, Y. et al. Notch signaling controls liver development by regulating biliary differentiation. Development 136, 1727–1739 (2009).

Article