HOXB6启动人胚胎干细胞向中胚层分化  

HOXB6 Initiates Differentiation of Human Embryonic Stem Cells into Mesoderm

作　　者：陈肖源 温玉琪 夏美娟 王洪涛 王梦鸽 周家喜 CHEN Xiaoyuan;WEN Yuqi;XIA Meijuan;WANG Hongtao;WANG Mengge;ZHOU Jiaxi(Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所)实验血液学国家重点实验室国家血液系统疾病临床医学研究中心,天津300020

出　　处：《中国细胞生物学学报》2020年第6期962-971,共10页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81530008)资助的课题。

摘　　要：HOXB6在胚胎发育过程中发挥重要作用,但在人胚胎干细胞中胚层分化中的作用尚不清楚。该研究利用人胚胎干细胞中胚层分化模型结合RNA-seq分析发现,HOXB6在中胚层分化过程中显著上调,敲降HOXB6的表达抑制人胚胎干细胞向中胚层分化,提示HOXB6在中胚层分化过程中发挥功能。通过建立HOXB6诱导性过表达的人胚胎干细胞株发现,HOXB6过表达抑制人胚胎干细胞多能性标志分子的表达,并且显著上调中胚层标志分子的表达。该研究表明,HOXB6单独过表达能够启动人胚胎干细胞向中胚层分化,为理解人类早期发育和建立人胚胎干细胞高效诱导分化体系提供了理论依据。Although HOXB6 plays an important role in embryonic development,its function in the mesoderm differentiation of hESCs(human embryonic stem cells)remains unclear.In this study,by taking advantage of hESC mesoderm differentiation model and RNA-seq analysis,HOXB6 was found to be significantly up-regulated during the mesoderm differentiation of hESCs.In addition,HOXB6 depletion inhibited the mesoderm differentiation of hESCs,implying that HOXB6 was implicated in mesoderm differentiation.Through establishing a DOX(doxcycline)inducible HOXB6-overexpressed hESC lines,this study found that the enforced expression of HOXB6 leaded to a significant downregulation of pluripotency markers,while dramatically increased the expression of mesoderm markers.This study reveals that HOXB6 over-expression suffices to induce mesoderm differentiation in hESCs,providing a theoretical basis for understanding human early development and establishing an efficient differentiation system of hESCs.

关 键 词：人胚胎干细胞 中胚层分化 HOXB6 

分 类 号：R321[医药卫生—人体解剖和组织胚胎学]