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Study of WNT Signaling During Endode...

Tan, Chunlai.

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Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells./
Author:	Tan, Chunlai.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	145 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-08, Section: B.
Contained By:	Dissertations Abstracts International80-08B.
Subject:	Biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13837890
ISBN:	9780438851887

Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells.
Tan, Chunlai.

Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 145 p.

Source: Dissertations Abstracts International, Volume: 80-08, Section: B.

Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2018.

This item must not be sold to any third party vendors.

WNT signaling is essential during definitive endoderm (DE) formation in sea urchin, zebrafish, Xenopus and mouse in vivo. It is also important for DE differentiation of human embryonic stem cells (ESCs), but the mechanism is largely unknown. In this study, we used three-day DE differentiation from human ESCs line H1 as in vitro model to investigate how WNT signaling pathways, including canonical and non-canonical WNT signaling pathways, regulates human DE formation. Blocking canonical WNT signaling by chemical inhibitors XAV939 and IWP-2 leads to abnormal morphology change during DE differentiation, and sharply decrease of endoderm markers FOXA2 and SOX17 expression. We also knocked out CTNNB1 by CRISPR/Cas9 technology. The CTNNB1-/- clones maintained normal characteristics of human ESCs, but failed to differentiate to DE and showed abnormal morphology during DE differentiation. FOXA2 and SOX17 were also sharply decreased at mRNA level, and became undetectable at protein level. Importantly, overexpression of CTNNB1 in these KO cells rescued the DE differentiation. Altogether, these results prove that canonical WNT signaling is essential during DE differentiation. Furthermore, we also blocked non-canonical WNT signaling by its chemical inhibitors SP600125 (block partial WNT/PCP) and CsA (block partial WNT/Ca 2+). We found that these treatments impair DE differentiation, suggested by abnormal morphology change and decrease of FOXA2 and SOX17. DVL is a conserve central mediator of both canonical and non-canonical WNT signaling pathways. Overexpression of DEP domain of DVL blocks non-canonical WNT signaling. HA-DEP-ires-GFP H1 cell line was generated. During DE differentiation, their morphology changes abnormally, and FOXA2 and SOX17 sharply decreased. These results suggest that non-canonical WNT is also involved in DE differentiation. In conclusion, both canonical and non-canonical WNT signaling pathways are required for DE differentiation.

ISBN: 9780438851887Subjects--Topical Terms:

522710
Biology.

Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells.
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520 $a WNT signaling is essential during definitive endoderm (DE) formation in sea urchin, zebrafish, Xenopus and mouse in vivo. It is also important for DE differentiation of human embryonic stem cells (ESCs), but the mechanism is largely unknown. In this study, we used three-day DE differentiation from human ESCs line H1 as in vitro model to investigate how WNT signaling pathways, including canonical and non-canonical WNT signaling pathways, regulates human DE formation. Blocking canonical WNT signaling by chemical inhibitors XAV939 and IWP-2 leads to abnormal morphology change during DE differentiation, and sharply decrease of endoderm markers FOXA2 and SOX17 expression. We also knocked out CTNNB1 by CRISPR/Cas9 technology. The CTNNB1-/- clones maintained normal characteristics of human ESCs, but failed to differentiate to DE and showed abnormal morphology during DE differentiation. FOXA2 and SOX17 were also sharply decreased at mRNA level, and became undetectable at protein level. Importantly, overexpression of CTNNB1 in these KO cells rescued the DE differentiation. Altogether, these results prove that canonical WNT signaling is essential during DE differentiation. Furthermore, we also blocked non-canonical WNT signaling by its chemical inhibitors SP600125 (block partial WNT/PCP) and CsA (block partial WNT/Ca 2+). We found that these treatments impair DE differentiation, suggested by abnormal morphology change and decrease of FOXA2 and SOX17. DVL is a conserve central mediator of both canonical and non-canonical WNT signaling pathways. Overexpression of DEP domain of DVL blocks non-canonical WNT signaling. HA-DEP-ires-GFP H1 cell line was generated. During DE differentiation, their morphology changes abnormally, and FOXA2 and SOX17 sharply decreased. These results suggest that non-canonical WNT is also involved in DE differentiation. In conclusion, both canonical and non-canonical WNT signaling pathways are required for DE differentiation.
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