- Title Information
- Title
- Transdifferentiation of liver to pancreas
- Name:
Personal
- Name Part
- Srivastava, Akash
- Role
- Role Term:
Text
- creator
- Origin Information
- Copyright Date
- 2015
- Physical Description
- Extent
- 15, 177 p.
- digitalOrigin
- born digital
- Note
- Thesis (Ph.D. -- Brown University (2015)
- Name:
Personal
- Name Part
- Horb, Marko
- Role
- Role Term:
Text
- Director
- Name:
Personal
- Name Part
- Freiman, Richard
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Morrow, Eric
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Wharton, Kristi
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Zorn, Aaron
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. BIOMED: Molecular Biology, Cell Biology, and Biochemistry
- Role
- Role Term:
Text
- sponsor
- Genre (aat)
- theses
- Abstract
- Diabetes mellitus results from gradual decline in pancreatic beta cell mass and function. Cell-based therapies in diabetes research are mainly focused on using stem cells to produce pancreatic beta cells in vitro for transplantation. A promising alternative strategy is to generate pancreatic tissue from other tissues already present in the body by
transdifferentiation. Liver provides the best alternative source of tissue to create ectopic
pancreatic tissue because liver has the highest regenerative capacity among all
parenchymal organs and only few key developmental steps specify liver and pancreatic lineages during organogenesis. To this end, transdifferentiation of liver to pancreas has been reported in different systems but the molecular mechanism of this process is currently unknown.
Using transgenic Xenopus tadpoles we previously showed that Pdx1-VP16 converts liver cells into all pancreatic cell types (both endocrine and exocrine), while Ptf1a-VP16
converts liver cells to only acinar (exocrine) cells. However, which genes are activated by
Pdx1-VP16 or Ptf1a-VP16 in this process is unknown. In order to gain insight into the
gene regulatory networks controlled by Pdx1-VP16 and Ptf1a-VP16 during the
transdifferentiation of liver to pancreas, we performed a microarray analysis and
compared the gene expression profile of transgenic tadpoles with that of control tadpoles.
We found upregulation of β-catenin inhibitor Chibby homolog1 (Cby) in Ptf1a-VP16
microarray. We demonstrated that cby is expressed in transdifferentiated livers of Ptf1aVP16 transgenic tadpoles and also in developing foregut organs (stomach/duodenum and pancreas) in wild-type Xenopus embryos. By overexpressing cby in Xenopus transgenic tadpole livers at NF 44-45, we demonstrated that expression of cby converts tadpole liver to ectopic endocrine pancreas, whereas using gain-of-function and loss-of-function experiments in early endoderm of wild-type Xenopus embryos we showed that cby promotes the formation of exocrine pancreas during normal pancreas development. Further analyses of these phenotypes indicated that inhibition of β-catenin might have two different roles in early versus late pancreas development. A better understanding of the molecular mechanism involved in transdifferentiation of liver to pancreas would enable researchers to create functional pancreatic beta cells from liver cells for thetreatment of diabetes.
- Subject
- Topic
- Transdifferentiation
- Subject
- Topic
- Pdx1-VP16
- Subject
- Topic
- Ptf1a-VP16
- Subject
- Topic
- Chibby
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1000617")
- Topic
- Liver
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1051970")
- Topic
- Pancreas
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20150601
- Language
- Language Term:
Code (ISO639-2B)
- eng
- Language Term:
Text
- English
- Identifier:
DOI
- 10.7301/Z0Z60MF3
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations