Spatial Patterning of Liver Progenitor Cell Differentiation Mediated by Cellular Contractility and Notch Signaling

Overview

Journal Elife

Specialty Biology

Date 2018 Dec 28

PMID 30589410

Citations 20

Authors

Kerim B Kaylan

Ian C Berg

Matthew J Biehl

Aidan Brougham-Cook

Ishita Jain

Sameed M Jamil

Lauren H Sargeant

Nicholas J Cornell

Lori T Raetzman

Gregory H Underhill

Affiliations

Soon will be listed here.

Abstract

The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to the established roles of TGFβ and Notch signaling in this fate specification process, there is increasing evidence that liver progenitors are sensitive to mechanical cues. Here, we utilized microarrayed patterns to provide a controlled biochemical and biomechanical microenvironment for mouse liver progenitor cell differentiation. In these defined circular geometries, we observed biliary differentiation at the periphery and hepatocytic differentiation in the center. Parallel measurements obtained by traction force microscopy showed substantial stresses at the periphery, coincident with maximal biliary differentiation. We investigated the impact of downstream signaling, showing that peripheral biliary differentiation is dependent not only on Notch and TGFβ but also E-cadherin, myosin-mediated cell contractility, and ERK. We have therefore identified distinct combinations of microenvironmental cues which guide fate specification of mouse liver progenitors toward both hepatocyte and biliary fates.

Citing Articles

Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.

Bebelman M, Belicova L, Gralinska E, Jumel T, Lahree A, Sommer S Development. 2024; 151(22).

PMID: 39373104 PMC: 11607689. DOI: 10.1242/dev.202777.

Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications.

Ryoo H, Kimmel H, Rondo E, Underhill G Bioeng Transl Med. 2024; 9(3):e10627.

PMID: 38818120 PMC: 11135158. DOI: 10.1002/btm2.10627.

Regulatory role of cholesterol in modulating actin dynamics and cell adhesive interactions in the trabecular meshwork.

Wang T, Kimmel H, Park C, Ryoo H, Liu J, Underhill G bioRxiv. 2024; .

PMID: 38352310 PMC: 10862777. DOI: 10.1101/2024.02.02.578717.

Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity.

Urman M, John N, Jung T, Lee C Biol Open. 2023; 13(1).

PMID: 38156664 PMC: 10810562. DOI: 10.1242/bio.060261.

Spatial Single Cell Analysis of Proteins in 2D Human Gastruloids Using Iterative Immunofluorescence.

Freeburne E, Teague S, Khan H, Li B, Ding S, Chen B Curr Protoc. 2023; 3(10):e915.

PMID: 37882990 PMC: 11132115. DOI: 10.1002/cpz1.915.

References

Ober E, Lemaigre F . Development of the liver: Insights into organ and tissue morphogenesis. J Hepatol. 2018; 68(5):1049-1062. DOI: 10.1016/j.jhep.2018.01.005. View

Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M . Role of YAP/TAZ in mechanotransduction. Nature. 2011; 474(7350):179-83. DOI: 10.1038/nature10137. View

Nelson C, Jean R, Tan J, Liu W, Sniadecki N, Spector A . Emergent patterns of growth controlled by multicellular form and mechanics. Proc Natl Acad Sci U S A. 2005; 102(33):11594-9. PMC: 1187971. DOI: 10.1073/pnas.0502575102. View

Brafman D, Chien S, Willert K . Arrayed cellular microenvironments for identifying culture and differentiation conditions for stem, primary and rare cell populations. Nat Protoc. 2012; 7(4):703-17. DOI: 10.1038/nprot.2012.017. View

Oda T, Elkahloun A, Pike B, Okajima K, Krantz I, Genin A . Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997; 16(3):235-42. DOI: 10.1038/ng0797-235. View

Kodama Y, Hijikata M, Kageyama R, Shimotohno K, Chiba T . The role of notch signaling in the development of intrahepatic bile ducts. Gastroenterology. 2004; 127(6):1775-86. DOI: 10.1053/j.gastro.2004.09.004. View

Roskams T, Theise N, Balabaud C, Bhagat G, Bhathal P, Bioulac-Sage P . Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology. 2004; 39(6):1739-45. DOI: 10.1002/hep.20130. View

Desai S, Tung J, Zhou V, Grenert J, Malato Y, Rezvani M . Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. Hepatology. 2016; 64(1):261-75. PMC: 5224931. DOI: 10.1002/hep.28450. View

Tarlow B, Finegold M, Grompe M . Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. Hepatology. 2014; 60(1):278-89. PMC: 4077948. DOI: 10.1002/hep.27084. View

10.

Vincent T, Neve E, Johnson J, Kukalev A, Rojo F, Albanell J . A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol. 2009; 11(8):943-50. PMC: 3769970. DOI: 10.1038/ncb1905. View

11.

Yimlamai D, Christodoulou C, Galli G, Yanger K, Pepe-Mooney B, Gurung B . Hippo pathway activity influences liver cell fate. Cell. 2014; 157(6):1324-1338. PMC: 4136468. DOI: 10.1016/j.cell.2014.03.060. View

12.

Aujla P, Bogdanovic V, Naratadam G, Raetzman L . Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure. Dev Dyn. 2015; 244(8):921-34. PMC: 4520742. DOI: 10.1002/dvdy.24283. View

13.

Kourouklis A, Kaylan K, Underhill G . Substrate stiffness and matrix composition coordinately control the differentiation of liver progenitor cells. Biomaterials. 2016; 99:82-94. DOI: 10.1016/j.biomaterials.2016.05.016. View

14.

Yu F, Zhao B, Panupinthu N, Jewell J, Lian I, Wang L . Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 2012; 150(4):780-91. PMC: 3433174. DOI: 10.1016/j.cell.2012.06.037. View

15.

Yamamoto S, Charng W, Rana N, Kakuda S, Jaiswal M, Bayat V . A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands. Science. 2012; 338(6111):1229-32. PMC: 3663443. DOI: 10.1126/science.1228745. View

16.

Boulter L, Govaere O, Bird T, Radulescu S, Ramachandran P, Pellicoro A . Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med. 2012; 18(4):572-9. PMC: 3364717. DOI: 10.1038/nm.2667. View

17.

Flaim C, Chien S, Bhatia S . An extracellular matrix microarray for probing cellular differentiation. Nat Methods. 2005; 2(2):119-25. DOI: 10.1038/nmeth736. View

18.

Wildenberg G, Dohn M, Carnahan R, Davis M, Lobdell N, Settleman J . p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell. 2006; 127(5):1027-39. DOI: 10.1016/j.cell.2006.09.046. View

19.

Gouw A, Clouston A, Theise N . Ductular reactions in human liver: diversity at the interface. Hepatology. 2011; 54(5):1853-63. DOI: 10.1002/hep.24613. View

20.

Fabris L, Spirli C, Cadamuro M, Fiorotto R, Strazzabosco M . Emerging concepts in biliary repair and fibrosis. Am J Physiol Gastrointest Liver Physiol. 2017; 313(2):G102-G116. PMC: 5582882. DOI: 10.1152/ajpgi.00452.2016. View