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

Sox17 Regulates Dynamic Gene Regulat...

McDonald, Angela Christine Hiltunen.

FindBook

Google Book

Amazon

博客來

Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells./
作者:	McDonald, Angela Christine Hiltunen.
面頁冊數:	171 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-01(E), Section: B.
Contained By:	Dissertation Abstracts International77-01B(E).
標題:	Developmental biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3719564
ISBN:	9781339000893

Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells.
McDonald, Angela Christine Hiltunen.

Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells. - 171 p.

Source: Dissertation Abstracts International, Volume: 77-01(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2015.

The gene regulatory networks (GRNs) driving mammalian extraembryonic endoderm (ExEn) and definitive endoderm (DE) specification are not well understood. To extend our understanding of mammalian endoderm specification, we used high-throughput genomic approaches in combination with in vitro gain of function studies to investigate the regulatory interactions of the endoderm GRN candidate Sox17. In our first study, we overexpressed Sox17 in embryonic stem cells (ESCs), driving cell fate conversion to an ExEn stem (XEN) cell-like state (Sox17-XEN), equivalent to embryo-derived XEN cells. To elucidate the dynamic networks activated by Sox17 during XEN conversion, we overlaid 352 promoter occupancy datasets onto RNA-sequencing (RNA-seq) time-series expression data and identified putative ExEn cell fate regulators. We perturbed the expression of putative ExEn repressor Nr5a2, and confirmed its ability to repress ExEn differentiation in ESCs. Moreover, we predicted and tested the ability of Sox17 to drive XEN cell conversion by activating autoregulatory and feedforward GRN motifs. We found that Sox17 autoregulates its expression by binding its own promoter, and further assembles feedforward loops activating Gata4, Gata6 and Sall4 to drive XEN cell fate. In our second study, we overexpressed Sox17 in epiblast stem cells (EpiSCs), and in contrast to ESCs, induced mesendoderm fate, a precursor of DE. We overlaid Sox17 promoter occupancy data onto RNA-seq time-series data following Sox17 overexpression in ESCs and EpiSCs, and drafted putative Sox17 GRN motifs. In ESCs, Sox17 regulates ExEn genes including Cyp26a1, Lgals2 and Muc13 whereas Sox17 activates primitive streak genes Lhx1, Fgf8 and T in EpiSCs, driving ExEn and mesendoderm fate, respectively. Additionally, we predicted Sox17 GRN motifs conserved in both ExEn and mesendoderm, regulating the expression of pan-endoderm genes including Foxa2, Foxq1, and Spink3. Together these data suggest that Sox17 activates conserved core GRN motifs as well as tissue-specific GRN motifs to drive cell fate.

ISBN: 9781339000893Subjects--Topical Terms:

592588
Developmental biology.

Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells.
LDR:03072nmm a2200301 4500 001 2077547
005 20161114130326.5
008 170521s2015 ||||||||||||||||| ||eng d
020 $a 9781339000893
035 $a (MiAaPQ)AAI3719564
035 $a AAI3719564
040 $a MiAaPQ $c MiAaPQ
100 1 $a McDonald, Angela Christine Hiltunen. $3 3193056
245 1 0 $a Sox17 Regulates Dynamic Gene Regulatory Networks to Specify Cell Fates in Pluripotent Stem Cells.
300 $a 171 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-01(E), Section: B.
500 $a Includes supplementary digital materials.
500 $a Advisers: Janet Rossant; William L. Stanford.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2015.
520 $a The gene regulatory networks (GRNs) driving mammalian extraembryonic endoderm (ExEn) and definitive endoderm (DE) specification are not well understood. To extend our understanding of mammalian endoderm specification, we used high-throughput genomic approaches in combination with in vitro gain of function studies to investigate the regulatory interactions of the endoderm GRN candidate Sox17. In our first study, we overexpressed Sox17 in embryonic stem cells (ESCs), driving cell fate conversion to an ExEn stem (XEN) cell-like state (Sox17-XEN), equivalent to embryo-derived XEN cells. To elucidate the dynamic networks activated by Sox17 during XEN conversion, we overlaid 352 promoter occupancy datasets onto RNA-sequencing (RNA-seq) time-series expression data and identified putative ExEn cell fate regulators. We perturbed the expression of putative ExEn repressor Nr5a2, and confirmed its ability to repress ExEn differentiation in ESCs. Moreover, we predicted and tested the ability of Sox17 to drive XEN cell conversion by activating autoregulatory and feedforward GRN motifs. We found that Sox17 autoregulates its expression by binding its own promoter, and further assembles feedforward loops activating Gata4, Gata6 and Sall4 to drive XEN cell fate. In our second study, we overexpressed Sox17 in epiblast stem cells (EpiSCs), and in contrast to ESCs, induced mesendoderm fate, a precursor of DE. We overlaid Sox17 promoter occupancy data onto RNA-seq time-series data following Sox17 overexpression in ESCs and EpiSCs, and drafted putative Sox17 GRN motifs. In ESCs, Sox17 regulates ExEn genes including Cyp26a1, Lgals2 and Muc13 whereas Sox17 activates primitive streak genes Lhx1, Fgf8 and T in EpiSCs, driving ExEn and mesendoderm fate, respectively. Additionally, we predicted Sox17 GRN motifs conserved in both ExEn and mesendoderm, regulating the expression of pan-endoderm genes including Foxa2, Foxq1, and Spink3. Together these data suggest that Sox17 activates conserved core GRN motifs as well as tissue-specific GRN motifs to drive cell fate.
590 $a School code: 0779.
650 4 $a Developmental biology. $3 592588
650 4 $a Bioinformatics. $3 553671
650 4 $a Biomedical engineering. $3 535387
690 $a 0758
690 $a 0715
690 $a 0541
710 2 $a University of Toronto (Canada). $b Biomedical Engineering. $3 2101094
773 0 $t Dissertation Abstracts International $g 77-01B(E).
790 $a 0779
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3719564