分子细胞生物学报
分子細胞生物學報
분자세포생물학보
JOURNAL OF MOLECULAR CELL BIOLOGY
2009年
2期
127-136
,共10页
孙丽%王海震%张颖%刘定干
孫麗%王海震%張穎%劉定榦
손려%왕해진%장영%류정간
C/EBPβ%LIP%mES细胞%未分化状态
C/EBPβ%LIP%mES細胞%未分化狀態
C/EBPβ%LIP%mES세포%미분화상태
C/EBP. LIP. ES cells%undifferentiated state
C/EBPPB (CCAAT/增强子结合蛋白β,又称NF-IL6)是一个多功能的转录因子,其主要功能之一是促进细胞分化.白血病抑制因子(LIF)是一个细胞因子,其在不同类型的细胞中具有不同的效应:它诱导前脂肪细胞分化,却抑制小鼠胚多能干细胞(mES)的分化.在mES中,C/EBPβ究竟起什么作用,尚未有报道.本文首次报告在mES中,在LIF蛋白存在下,C/EBPβ的作用是维持mES的未分化状态.即C/EBPβ是LIF的调控对象.主要事实如下.在mES细胞中,内源C/EBPβ蛋白的表达量与加到培养基中的LIF蛋白的量呈正相关.而在未分化的mES细胞中人工高表达的外源C/EBPIs蛋白和其截短形式LIP蛋白,在LIF存在下,也不但不促进反而抑制mES细胞分化,C/EBPIs的大分子异型蛋白还显著促进mES细胞的增殖:而且,在LIF去除后.这种促进mES细胞增殖的效应还能持续一段短时间.当LIF不存在时.C/EBPIs和UP才如所预期的那样,诱导分化相关基因表达并促进细胞分化.C/EBPβ和LIP所调控的某些分化相关的基因的表达水平,当LIF存在时.也比没有LIF时显著降低.因此.在mES细胞中C/EBPIs是受LIF的调控而作为LIF的中介,维持mES于未分化状态.
C/EBPPB (CCAAT/增彊子結閤蛋白β,又稱NF-IL6)是一箇多功能的轉錄因子,其主要功能之一是促進細胞分化.白血病抑製因子(LIF)是一箇細胞因子,其在不同類型的細胞中具有不同的效應:它誘導前脂肪細胞分化,卻抑製小鼠胚多能榦細胞(mES)的分化.在mES中,C/EBPβ究竟起什麽作用,尚未有報道.本文首次報告在mES中,在LIF蛋白存在下,C/EBPβ的作用是維持mES的未分化狀態.即C/EBPβ是LIF的調控對象.主要事實如下.在mES細胞中,內源C/EBPβ蛋白的錶達量與加到培養基中的LIF蛋白的量呈正相關.而在未分化的mES細胞中人工高錶達的外源C/EBPIs蛋白和其截短形式LIP蛋白,在LIF存在下,也不但不促進反而抑製mES細胞分化,C/EBPIs的大分子異型蛋白還顯著促進mES細胞的增殖:而且,在LIF去除後.這種促進mES細胞增殖的效應還能持續一段短時間.噹LIF不存在時.C/EBPIs和UP纔如所預期的那樣,誘導分化相關基因錶達併促進細胞分化.C/EBPβ和LIP所調控的某些分化相關的基因的錶達水平,噹LIF存在時.也比沒有LIF時顯著降低.因此.在mES細胞中C/EBPIs是受LIF的調控而作為LIF的中介,維持mES于未分化狀態.
C/EBPPB (CCAAT/증강자결합단백β,우칭NF-IL6)시일개다공능적전록인자,기주요공능지일시촉진세포분화.백혈병억제인자(LIF)시일개세포인자,기재불동류형적세포중구유불동적효응:타유도전지방세포분화,각억제소서배다능간세포(mES)적분화.재mES중,C/EBPβ구경기십요작용,상미유보도.본문수차보고재mES중,재LIF단백존재하,C/EBPβ적작용시유지mES적미분화상태.즉C/EBPβ시LIF적조공대상.주요사실여하.재mES세포중,내원C/EBPβ단백적표체량여가도배양기중적LIF단백적량정정상관.이재미분화적mES세포중인공고표체적외원C/EBPIs단백화기절단형식LIP단백,재LIF존재하,야불단불촉진반이억제mES세포분화,C/EBPIs적대분자이형단백환현저촉진mES세포적증식:이차,재LIF거제후.저충촉진mES세포증식적효응환능지속일단단시간.당LIF불존재시.C/EBPIs화UP재여소예기적나양,유도분화상관기인표체병촉진세포분화.C/EBPβ화LIP소조공적모사분화상관적기인적표체수평,당LIF존재시.야비몰유LIF시현저강저.인차.재mES세포중C/EBPIs시수LIF적조공이작위LIF적중개,유지mES우미분화상태.
C/EBPIs(also called NF-IL6)iS a multifunctional transcription factor,a major function of which iS the enhancement of cellular differentiation.Leukemia inhibitory factor(LIF)is a cytokine playing divergent roles in different cell types:induces differentiation in preadipocytes and,however,inhibits differentiation in pluripotent murine embryonic stem(mES)cells.However,roles of C/EBPβ in mES cells are obscure.Here.we show for the first time that C/EBPβ in the presence of LIF plays a role of sustaining undifferentiated state in this cell line.i.e.C/EBPIs is a target of regulation of LIF,as described as follows.The expression of endogenous C/EBPβproteins in mES ceils is positively correlated with the LIF added into medium.Even the exogenous C/EBPβproteins and their truncated form.LIP,artificially overexpressed in undifferentiated mES cells,do not enhance but inhibit ES cells'differentiation in the presence of LIF,and the long isoforIBS of C/EBPIs proteins strongly enhance cell propagation.This enhancement lasts for a certain short time even after LIF removal. In the absence of LIF, C/EBPβ and LIP induce expression of differentiation-related genes and promote mES cells' differentiation, as anticipated. With LIF, the expression levels of some differentiation-related genes regulated by C/EBPβ and LIP were significantly lower than that without LIF. Therefore, in pluripotent mES cells C/EBPβ is regulated by LIF and sustains undifferentiated state of those cells as a mediator of LIF.
