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The role of SOX9 in mammary gland de...

Malhotra, Gautam K.

The role of SOX9 in mammary gland development and stem/progenitor cell maintenance.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of SOX9 in mammary gland development and stem/progenitor cell maintenance.
作者:	Malhotra, Gautam K.
面頁冊數:	289 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
附註:	Adviser: Vimla Band.
Contained By:	Dissertation Abstracts International75-05B(E).
標題:	Cellular biology.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3578520
ISBN:	9781303722936

The role of SOX9 in mammary gland development and stem/progenitor cell maintenance.
Malhotra, Gautam K.

The role of SOX9 in mammary gland development and stem/progenitor cell maintenance. - 289 p.

Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.

Thesis (Ph.D.)--University of Nebraska Medical Center, 2013.

This item is not available from ProQuest Dissertations & Theses.

Recent advances in the field of breast cancer research have resulted in the identification of cancer stem cells (CSCs) within breast tumors. These CSCs retain properties of normal mammary stem cells (MaSCs) and are responsible for the initiation and propagation of the tumor. While breast CSCs and normal MaSCs share many characteristics, details of normal MaSC regulation have not been well defined. To identify regulatory factors important for MaSCs, we compared gene expression profiles of bipotent MaSCs with differentiated myoepithelial cells to establish a gene set enriched within the MaSC population. Using unsupervised hierarchical clustering, we then compared the MaSC gene signature with expression profiles of the five intrinsic breast cancer subtypes to identify a cluster of genes specifically expressed in both normal MaSCs and the basal-like subtype of breast cancer. From this analysis, Sox9 emerged as a potential regulator of MaSC function.

ISBN: 9781303722936Subjects--Topical Terms:

708607
Cellular biology.

The role of SOX9 in mammary gland development and stem/progenitor cell maintenance.
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245 1 4 $a The role of SOX9 in mammary gland development and stem/progenitor cell maintenance.
300 $a 289 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
500 $a Adviser: Vimla Band.
502 $a Thesis (Ph.D.)--University of Nebraska Medical Center, 2013.
506 $a This item is not available from ProQuest Dissertations & Theses.
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 Recent advances in the field of breast cancer research have resulted in the identification of cancer stem cells (CSCs) within breast tumors. These CSCs retain properties of normal mammary stem cells (MaSCs) and are responsible for the initiation and propagation of the tumor. While breast CSCs and normal MaSCs share many characteristics, details of normal MaSC regulation have not been well defined. To identify regulatory factors important for MaSCs, we compared gene expression profiles of bipotent MaSCs with differentiated myoepithelial cells to establish a gene set enriched within the MaSC population. Using unsupervised hierarchical clustering, we then compared the MaSC gene signature with expression profiles of the five intrinsic breast cancer subtypes to identify a cluster of genes specifically expressed in both normal MaSCs and the basal-like subtype of breast cancer. From this analysis, Sox9 emerged as a potential regulator of MaSC function.
520 $a Using an in vitro differentiation assay, we have shown Sox9 is expressed in bipotent MaSCs; however, its expression is lost upon differentiation into either the luminal or myoepithelial cell lineages. To verify the expression of Sox9 in bipotent MaSCs we used embryonic in vivo lineage tracing to demonstrate Sox9 expressing MaSCs are responsible for generating the entire mammary gland. Postnatally, short pulse chase tracing experiments demonstrate Sox9 expression is limited to luminal progenitors and a rare population of basal stem cells. Notably, over time, the Sox9+ cells give rise to differentiated progeny of all cell lineages.
520 $a Moreover, a functional role for Sox9 in maintaining the stem/progenitor compartment was demonstrated by Sox9 conditional knockout (cKO) which results in early developmental defects of ductal branching and outgrowth. Finally, Sox9 cKO fate mapping revealed a loss of Sox9 deleted cells from the luminal compartment suggesting an essential role in luminal, but not myoepithelial, lineage commitment. These studies identify Sox9 as a key regulator of stem and progenitor cell maintenance and define its position within the mammary epithelial cell hierarchy.
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