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Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation

Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation
Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation

In the liver, ductal cells rarely proliferate during homeostasis but do so transiently after tissue injury. These cells can be expanded as organoids that recapitulate several of the cell-autonomous mechanisms of regeneration but lack the stromal interactions of the native tissue. Here, using organoid co-cultures that recapitulate the ductal-to-mesenchymal cell architecture of the portal tract, we demonstrate that a subpopulation of mouse periportal mesenchymal cells exerts dual control on proliferation of the epithelium. Ductal cell proliferation is either induced and sustained or, conversely, completely abolished, depending on the number of direct mesenchymal cell contacts, through a mechanism mediated, at least in part, by Notch signaling. Our findings expand the concept of the cellular niche in epithelial tissues, whereby not only soluble factors but also cell-cell contacts are the key regulatory cues involved in the control of cellular behaviors, suggesting a critical role for cell-cell contacts during regeneration.

1934-5909
Cordero-Espinoza, Lucía
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Dowbaj, Anna M
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Kohler, Timo N
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Strauss, Bernhard
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Sarlidou, Olga
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Belenguer, German
c5dbecdc-996c-46e5-83b4-714ad6c2f0d5
Pacini, Clare
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Martins, Nuno P
a982ca9e-5ad6-471b-91ca-c749cb1f90a6
Dobie, Ross
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Wilson-Kanamori, John R
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Butler, Richard
d7ae47e9-a7eb-4c63-8a47-c03a7736f26c
Prior, Nicole
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Serup, Palle
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Jug, Florian
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Henderson, Neil C
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Hollfelder, Florian
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Huch, Meritxell
defdc21f-6ca2-4a97-ab38-436adce9d37c
Cordero-Espinoza, Lucía
a5d62472-e4ae-43c9-a6dc-b572f8560e26
Dowbaj, Anna M
bcc5944c-e1c5-42cf-90d0-de20f550ddce
Kohler, Timo N
f80bc368-6503-4708-a5e7-fbe8a6f80982
Strauss, Bernhard
fb9f9f8e-415c-4ad1-9355-cb86cb6ba53c
Sarlidou, Olga
eb963452-474d-4054-8f85-e11fd4709752
Belenguer, German
c5dbecdc-996c-46e5-83b4-714ad6c2f0d5
Pacini, Clare
aedd6b0b-54c8-49fb-a4ff-df17592ca460
Martins, Nuno P
a982ca9e-5ad6-471b-91ca-c749cb1f90a6
Dobie, Ross
6b1ca3f4-7a9e-4279-a648-1040db24c442
Wilson-Kanamori, John R
88424a4f-a5ab-46b7-bd6b-3bdfb61dcea8
Butler, Richard
d7ae47e9-a7eb-4c63-8a47-c03a7736f26c
Prior, Nicole
27851f03-6041-4409-a15c-a2a164b883e0
Serup, Palle
f6fe6640-7d95-4987-b4dd-7289d6a7b530
Jug, Florian
8d50d111-94f4-4eac-8aee-79d8163d4d11
Henderson, Neil C
31a6faf3-f34d-4028-a36a-7fe7f1a30ab5
Hollfelder, Florian
a9f01280-f05d-4057-b5d7-85eac249e477
Huch, Meritxell
defdc21f-6ca2-4a97-ab38-436adce9d37c

Cordero-Espinoza, Lucía, Dowbaj, Anna M, Kohler, Timo N, Strauss, Bernhard, Sarlidou, Olga, Belenguer, German, Pacini, Clare, Martins, Nuno P, Dobie, Ross, Wilson-Kanamori, John R, Butler, Richard, Prior, Nicole, Serup, Palle, Jug, Florian, Henderson, Neil C, Hollfelder, Florian and Huch, Meritxell (2021) Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation. Cell Stem Cell. (doi:10.1016/j.stem.2021.07.002).

Record type: Article

Abstract

In the liver, ductal cells rarely proliferate during homeostasis but do so transiently after tissue injury. These cells can be expanded as organoids that recapitulate several of the cell-autonomous mechanisms of regeneration but lack the stromal interactions of the native tissue. Here, using organoid co-cultures that recapitulate the ductal-to-mesenchymal cell architecture of the portal tract, we demonstrate that a subpopulation of mouse periportal mesenchymal cells exerts dual control on proliferation of the epithelium. Ductal cell proliferation is either induced and sustained or, conversely, completely abolished, depending on the number of direct mesenchymal cell contacts, through a mechanism mediated, at least in part, by Notch signaling. Our findings expand the concept of the cellular niche in epithelial tissues, whereby not only soluble factors but also cell-cell contacts are the key regulatory cues involved in the control of cellular behaviors, suggesting a critical role for cell-cell contacts during regeneration.

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More information

e-pub ahead of print date: 28 July 2021

Identifiers

Local EPrints ID: 450950
URI: http://eprints.soton.ac.uk/id/eprint/450950
ISSN: 1934-5909
PURE UUID: e2824242-b765-416f-ba4c-b262d896ccf3
ORCID for Nicole Prior: ORCID iD orcid.org/0000-0003-2856-7052

Catalogue record

Date deposited: 25 Aug 2021 16:32
Last modified: 16 Nov 2021 03:06

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Contributors

Author: Lucía Cordero-Espinoza
Author: Anna M Dowbaj
Author: Timo N Kohler
Author: Bernhard Strauss
Author: Olga Sarlidou
Author: German Belenguer
Author: Clare Pacini
Author: Nuno P Martins
Author: Ross Dobie
Author: John R Wilson-Kanamori
Author: Richard Butler
Author: Nicole Prior ORCID iD
Author: Palle Serup
Author: Florian Jug
Author: Neil C Henderson
Author: Florian Hollfelder
Author: Meritxell Huch

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