发育医学电子杂志
髮育醫學電子雜誌
발육의학전자잡지
Journal of Developmental Medicine (Electronic Version)
2014年
3期
139-145
,共7页
张倩%宋斌峰%万扬%张昭军%鲍丙浩%谢尚论%刘汉芝%竺晓凡%袁卫平%贾海波%方向东
張倩%宋斌峰%萬颺%張昭軍%鮑丙浩%謝尚論%劉漢芝%竺曉凡%袁衛平%賈海波%方嚮東
장천%송빈봉%만양%장소군%포병호%사상론%류한지%축효범%원위평%가해파%방향동
纯红细胞再生障碍性贫血%microRNA%Rps19%p53%RNA-seq%斑马鱼
純紅細胞再生障礙性貧血%microRNA%Rps19%p53%RNA-seq%斑馬魚
순홍세포재생장애성빈혈%microRNA%Rps19%p53%RNA-seq%반마어
Diamond-blackfan anemia%microRNA%Rps19%p53%RNA-seq%Zebrafish
目的：探讨先天性纯红细胞再生障碍性贫血（DBA）相关 microRNA 的表达特征及其调控机制。方法利用 morpholino 技术建立核糖体蛋白基因 Rps19表达不足的 DBA 斑马鱼模型和Rps19与 p53同时表达不足的斑马鱼模型，利用新一代高通量测序（RNA-seq）技术，研究 DBA 斑马鱼模型的 microRNA 表达谱的特征及 p53在其中的调控作用。结果Rps19 MO 的斑马鱼胚胎的循环血细胞明显减少，且尾部呈现出向腹侧弯曲的异常形态。而在 p53敲低之后，斑马鱼的形态异常得到了一定程度的恢复。通过对 microRNA 表达谱的比较分析发现，在 Rps19不足的斑马鱼胚胎中约1/4的 microRNA 表达量显著偏低，这些异常表达的 microRNA 可能影响到斑马鱼的正常发育过程。而在 p53敲低之后，部分 microRNA 的表达恢复到正常水平。最终确定了47个在 DBA 发病过程中可能受 p53调控的 microRNA。结论DBA 斑马鱼模型的 microRNA 普遍低表达，其中部分 microRNA 受到 p53的表达水平的调控。
目的：探討先天性純紅細胞再生障礙性貧血（DBA）相關 microRNA 的錶達特徵及其調控機製。方法利用 morpholino 技術建立覈糖體蛋白基因 Rps19錶達不足的 DBA 斑馬魚模型和Rps19與 p53同時錶達不足的斑馬魚模型，利用新一代高通量測序（RNA-seq）技術，研究 DBA 斑馬魚模型的 microRNA 錶達譜的特徵及 p53在其中的調控作用。結果Rps19 MO 的斑馬魚胚胎的循環血細胞明顯減少，且尾部呈現齣嚮腹側彎麯的異常形態。而在 p53敲低之後，斑馬魚的形態異常得到瞭一定程度的恢複。通過對 microRNA 錶達譜的比較分析髮現，在 Rps19不足的斑馬魚胚胎中約1/4的 microRNA 錶達量顯著偏低，這些異常錶達的 microRNA 可能影響到斑馬魚的正常髮育過程。而在 p53敲低之後，部分 microRNA 的錶達恢複到正常水平。最終確定瞭47箇在 DBA 髮病過程中可能受 p53調控的 microRNA。結論DBA 斑馬魚模型的 microRNA 普遍低錶達，其中部分 microRNA 受到 p53的錶達水平的調控。
목적：탐토선천성순홍세포재생장애성빈혈（DBA）상관 microRNA 적표체특정급기조공궤제。방법이용 morpholino 기술건립핵당체단백기인 Rps19표체불족적 DBA 반마어모형화Rps19여 p53동시표체불족적반마어모형，이용신일대고통량측서（RNA-seq）기술，연구 DBA 반마어모형적 microRNA 표체보적특정급 p53재기중적조공작용。결과Rps19 MO 적반마어배태적순배혈세포명현감소，차미부정현출향복측만곡적이상형태。이재 p53고저지후，반마어적형태이상득도료일정정도적회복。통과대 microRNA 표체보적비교분석발현，재 Rps19불족적반마어배태중약1/4적 microRNA 표체량현저편저，저사이상표체적 microRNA 가능영향도반마어적정상발육과정。이재 p53고저지후，부분 microRNA 적표체회복도정상수평。최종학정료47개재 DBA 발병과정중가능수 p53조공적 microRNA。결론DBA 반마어모형적 microRNA 보편저표체，기중부분 microRNA 수도 p53적표체수평적조공。
Objective To characterize the genome-wide microRNA profile and to explore the biological functions and probable mechanisms for microRNAs in diamond-blackfan anemia (DBA). Method Zebrafish embryos at the one-cell stage were injected with the Rps19 MO and Rps19+p53 MO. The miRNomes of these zebrafish models and control, generated by miRNA-seq, were compared for determining the microRNA profile characteristics of DBA and regulatory function of p53. Result Rps19 morphants showed an obviously ventrally bent tail and a reduction in the circulating blood cells compared with the control embryos, which were partially rescued in Rps19+p53 MO at 48 hpf. By comparing the miRNomes with control, we found that about 25% of total expressed microRNAs in Rps19 MO had significantly lower expression, which might make an influence on the development process of Zebrafish embryos. The abnormal miRNomes were partially reversed by simultaneous knockdown of p53. We determined 47 microRNAs that were potentially regulated by p53 in DBA pathologic process.Conclusion microRNAs in Zebrafish model of DBA were in an inactive state, which was partially affected by p53.
