PMID- 27796316
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Oct 31
TI  - Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate 
      selection during liver injury.
PG  - 36077
LID - 10.1038/srep36077 [doi]
LID - 36077
AB  - Liver injury modulates local microenvironment, triggering production of signals 
      that instruct stem cell fate choices. In this study, we employed a microfluidic 
      co-culture system to recreate important interactions in the liver stem cell 
      niche, those between adult hepatocytes and liver progenitor cells (LPCs). We 
      demonstrate that pluripotent stem cell-derived LPCs choose hepatic fate when 
      cultured next to healthy hepatocytes but begin biliary differentiation program 
      when co-cultured with injured hepatocytes. We connect this fate selection to 
      skewing in production of hepatocyte growth factor (HGF) and transforming growth 
      factor (TGF)-beta1 caused by injury. Significantly, biliary fate selection of LPCs 
      was not observed in the absence of hepatocytes nor did it happen in the presence 
      of TGF-beta inhibitors. Our study demonstrates that microfluidic culture systems may 
      offer an interesting new tool for dissecting cellular interactions leading to 
      aberrant stem cell differentiation during injury.
FAU - Haque, Amranul
AU  - Haque A
AD  - Department of Biomedical Engineering, University of California Davis, CA 95616, 
      USA.
FAU - Gheibi, Pantea
AU  - Gheibi P
AD  - Department of Biomedical Engineering, University of California Davis, CA 95616, 
      USA.
FAU - Stybayeva, Gulnaz
AU  - Stybayeva G
AD  - Department of Biomedical Engineering, University of California Davis, CA 95616, 
      USA.
FAU - Gao, Yandong
AU  - Gao Y
AD  - Department of Biomedical Engineering, University of California Davis, CA 95616, 
      USA.
FAU - Torok, Natalie
AU  - Torok N
AD  - Department of Internal Medicine, University of California Davis, Sacramento, CA 
      95835, USA.
FAU - Revzin, Alexander
AU  - Revzin A
AD  - Department of Biomedical Engineering, University of California Davis, CA 95616, 
      USA.
LA  - eng
GR  - I01 BX002418/BX/BLRD VA/United States
GR  - P30 CA093373/CA/NCI NIH HHS/United States
GR  - R01 DK083283/DK/NIDDK NIH HHS/United States
GR  - R01 DK107255/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161031
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Keratin-7)
RN  - 0 (Serum Albumin)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 3K9958V90M (Ethanol)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Cell Lineage/*drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Ethanol/*toxicity
MH  - Hepatocyte Growth Factor/metabolism
MH  - Hepatocytes/*cytology/metabolism
MH  - Humans
MH  - Keratin-7/metabolism
MH  - Liver/cytology
MH  - Mice
MH  - Microfluidics/instrumentation/*methods
MH  - Microscopy, Fluorescence
MH  - Mouse Embryonic Stem Cells/cytology/drug effects/metabolism
MH  - Rats
MH  - Serum Albumin/analysis
MH  - Stem Cells/*cytology/drug effects/metabolism
MH  - Transforming Growth Factor beta1/antagonists & inhibitors/metabolism
PMC - PMC5086854
EDAT- 2016/11/01 06:00
MHDA- 2018/05/15 06:00
PMCR- 2016/10/31
CRDT- 2016/11/01 06:00
PHST- 2016/06/12 00:00 [received]
PHST- 2016/10/06 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
PHST- 2016/10/31 00:00 [pmc-release]
AID - srep36077 [pii]
AID - 10.1038/srep36077 [doi]
PST - epublish
SO  - Sci Rep. 2016 Oct 31;6:36077. doi: 10.1038/srep36077.