國家衛生研究院 NHRI:Item 3990099045/7298

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Title:	Transcriptional activation of FGF1 gene promoter sustains self-renewal of embryonic stem cells and neural stem cells through Aurora-A kinase signaling
Authors:	Hsu, YC;Kao, CY;Liu, JW;Chung, YF;Lee, DC;Chiu, IM
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Aurora-A kinase (AurA) is a centrosome and mitotic spindle- associated, cell cycle-regulated serine/threonine kinase and is a key regulator of asymmetric cell division and cell fate determination. Fibroblast growth factor 1 (FGF1) has been suggested as an important growth factor for many cell types. FGF1 and FGF-1B promoter (-540 to +31)-driven green fluorescent protein (F1BGFP) have been used to isolate neural stem/progenitor cells (NSPCs) and glioblastoma stem cells from developing mouse brains, human glioblastoma cell lines, and tissues, respectively. In this study, we provide several lines of evidence to demonstrate that AurA activation is required for self-renewal and multipotency in F1BGFP(+) stem cells: (i) Inhibition of AurA activation disrupted the maintenance of mouse embryonic stem cells (ESCs), mouse ESC-derived NSPCs, primary mouse brain NSPCs, and human glioblastoma stem cells; (ii) F1BGFP reporter could be used to isolate GFP(+) NSPCs with significantly higher levels of AurA activation, cell proliferation, and neurosphere formation; (iii) Autocrine/paracrine activation of AurA in F1BGFP(+) cells could be blocked by FGF1-neutralizing antibody, FGF receptor inhibitor SU5402, and AKT inhibitor; (iv) Inhibition of AurA activation reduced neurosphere formation of F1BGFP(+) NSPCs; (v) Markers of NSPC-multipotency also decreased upon AurA inhibition. These results suggest that AurA kinase regulates the growth and self-renewal of stem cells, such as ESCs and NSPCs. Using the F1BGFP reporter, we have provided a novel method to identify and enrich a subset of ESCs and NSPCs with AurA activation from different cellular and tissue sources.
Date:	2013-10
Relation:	Cell Transplantation. 2013 Oct;22(5):905.
Link to:	http://dx.doi.org/10.3727/096368913X664883
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0963-6897&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000318585300047
Appears in Collections:	[Ing-Ming Chiu] Conference Papers/Meeting Abstract

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