GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.

GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.
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DOI:
10.1126/sciadv.abg0834
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发表时间:
2022-03-11
期刊:
影响因子:
13.6
通讯作者:
Scott IC
Scott IC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Song M;Yuan X;Racioppi C;Leslie M;Stutt N;Aleksandrova A;Christiaen L;Wilson MD;Scott IC

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GATA4/5/6转录因子在心脏发育中起着重要的、保守的作用。为了了解GATA4/5/6如何调控中胚层到心脏的命运转变,我们标记、分离并对从斑马鱼原肠形成到体细胞发生的心脏前时间点表达GATA5的细胞进行了单细胞基因表达分析。我们发现,大多数中胚层来源的谱系都有GATA5/6的动态表达。在没有Gata5/6的情况下,中内胚层来源的细胞的群体结构发生了实质性的变化。除了预期的心脏中胚层缺失外,我们证实了伴随而来的颅咽中胚层扩张。此外,Gata5/6缺失导致心脏和咽部基因附近染色质可及性的广泛变化。斑马鱼和被囊状乔纳只有一个GATA4/5/6同源物的功能分析表明,GATA4/5/6作用于TBX1的上游,在促进心脏和抑制咽中胚层的识别方面发挥必要的细胞自主作用。总体而言,心脏和咽中胚层的命运选择是通过进化上保守的GATA4/5/6调控网络实现的。心脏和咽部命运的决定由古老的GATA4/5/6调节网络平衡。
GATA4/5/6 transcription factors play essential, conserved roles in heart development. To understand how GATA4/5/6 modulates the mesoderm-to-cardiac fate transition, we labeled, isolated, and performed single-cell gene expression analysis on cells that express gata5 at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was substantially altered. In addition to the expected absence of cardiac mesoderm, we confirmed a concomitant expansion of cranial-pharyngeal mesoderm. Moreover, Gata5/6 loss led to extensive changes in chromatin accessibility near cardiac and pharyngeal genes. Functional analyses in zebrafish and the tunicate Ciona, which has a single GATA4/5/6 homolog, revealed that GATA4/5/6 acts upstream of tbx1 to exert essential and cell-autonomous roles in promoting cardiac and inhibiting pharyngeal mesoderm identity. Overall, cardiac and pharyngeal mesoderm fate choices are achieved through an evolutionarily conserved GATA4/5/6 regulatory network. Cardiac and pharyngeal fate decisions are balanced by an ancient GATA4/5/6 regulatory network.
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