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- 01GPZN6KSMJGNBG350A9WW7SWD classification A1.
- 01GPZN6KSMJGNBG350A9WW7SWD date "2022".
- 01GPZN6KSMJGNBG350A9WW7SWD language "eng".
- 01GPZN6KSMJGNBG350A9WW7SWD type journalArticle.
- 01GPZN6KSMJGNBG350A9WW7SWD hasPart 01GQ08AYWQZXF045MFSM30BAW8.pdf.
- 01GPZN6KSMJGNBG350A9WW7SWD subject "Biology and Life Sciences".
- 01GPZN6KSMJGNBG350A9WW7SWD doi "10.1371/journal.pcbi.1009653".
- 01GPZN6KSMJGNBG350A9WW7SWD issn "1553-734X".
- 01GPZN6KSMJGNBG350A9WW7SWD issn "1553-7358".
- 01GPZN6KSMJGNBG350A9WW7SWD issue "2".
- 01GPZN6KSMJGNBG350A9WW7SWD volume "18".
- 01GPZN6KSMJGNBG350A9WW7SWD abstract "The initial step in bile duct development is the formation of a biliary lumen, a process which involves several cellular mechanisms, such as cell division and polarization, and secretion of fluid. However, how these mechanisms are orchestrated in time and space is difficult to understand. Here, we built a computational model of biliary lumen formation which represents every cell and its function in detail. With the model we can simulate the effect of biophysical aspects that affect duct formation. We have tested the individual and combined effects of directed cell division, apical constriction, and osmotic effects on lumen expansion by varying the parameters that control their relative strength. Our simulations suggest that successful bile duct lumen formation requires the simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size. Biliary ducts collect bile from liver lobules, the smallest functional and anatomical units of liver, and carry it to the gallbladder. Disruptions in this process caused by defective embryonic development, or through ductal reaction in liver disease have a major impact on life quality and survival of patients. A deep understanding of the processes underlying bile duct lumen formation is crucial to identify intervention points to avoid or treat the appearance of defective bile ducts. Several hypotheses have been proposed to characterize the biophysical mechanisms driving initial bile duct lumen formation during embryogenesis. Here, guided by the quantification of morphological features and expression of genes in bile ducts from embryonic mouse liver, we sharpened these hypotheses and collected data to develop a high resolution individual cell-based computational model that enables to test alternative hypotheses in silico. This model permits realistic simulations of tissue and cell mechanics at sub-cellular scale. Our simulations suggest that successful bile duct lumen formation requires a simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size.".
- 01GPZN6KSMJGNBG350A9WW7SWD author f8ab9005-fbe4-11ec-9205-f6e0b9d3c536.
- 01GPZN6KSMJGNBG350A9WW7SWD author urn:uuid:02d6259a-49e7-4716-9cb8-29420f83bc71.
- 01GPZN6KSMJGNBG350A9WW7SWD author urn:uuid:32933513-4003-47d7-ae92-09ecfdfcc237.
- 01GPZN6KSMJGNBG350A9WW7SWD author urn:uuid:a2b9e61e-2115-4680-9b3f-185cab67a078.
- 01GPZN6KSMJGNBG350A9WW7SWD author urn:uuid:bdd48c65-27b0-43b9-9668-5e6005f14eda.
- 01GPZN6KSMJGNBG350A9WW7SWD author urn:uuid:dceae85d-5fce-4152-bdfb-f73a6ef35cc4.
- 01GPZN6KSMJGNBG350A9WW7SWD dateCreated "2023-01-17T10:43:06Z".
- 01GPZN6KSMJGNBG350A9WW7SWD dateModified "2024-07-09T07:43:00Z".
- 01GPZN6KSMJGNBG350A9WW7SWD name "Quantitative modeling identifies critical cell mechanics driving bile duct lumen formation".
- 01GPZN6KSMJGNBG350A9WW7SWD pagination urn:uuid:ba46df2e-1577-478f-b75d-1b7f462739c6.
- 01GPZN6KSMJGNBG350A9WW7SWD sameAs LU-01GPZN6KSMJGNBG350A9WW7SWD.
- 01GPZN6KSMJGNBG350A9WW7SWD sourceOrganization urn:uuid:253da5e2-af5c-4cee-bee3-ff6795646435.
- 01GPZN6KSMJGNBG350A9WW7SWD type A1.