東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Study of WNT Signaling During Endode...

Tan, Chunlai.

FindBook

Google Book

Amazon

博客來

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

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells./
作者:	Tan, Chunlai.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	145 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-08, Section: B.
Contained By:	Dissertations Abstracts International80-08B.
標題:	Biology. -
電子資源:	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.
LDR:03103nmm a2200325 4500 001 2208034
005 20190929184033.5
008 201008s2018 ||||||||||||||||| ||eng d
020 $a 9780438851887
035 $a (MiAaPQ)AAI13837890
035 $a AAI13837890
040 $a MiAaPQ $c MiAaPQ
100 1 $a Tan, Chunlai. $3 3435044
245 1 0 $a Study of WNT Signaling During Endodermal Differentiation of Human Embryonic Stem Cells.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2018
300 $a 145 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-08, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2018.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
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.
590 $a School code: 1307.
650 4 $a Biology. $3 522710
650 4 $a Cellular biology. $3 3172791
650 4 $a Developmental biology. $3 592588
690 $a 0306
690 $a 0379
690 $a 0758
710 2 $a The Chinese University of Hong Kong (Hong Kong). $b Biomedical Sciences. $3 3435045
773 0 $t Dissertations Abstracts International $g 80-08B.
790 $a 1307
791 $a Ph.D.
792 $a 2018
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13837890