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Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation

机译：PBX4通过分区第二心脏场祖细胞并限制增殖来限制心脏尺寸和促进曲线动脉形成

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摘要

Vertebrate heart development requires the integration of temporally distinct differentiating progenitors. However, few signals are understood that restrict the size of the later-differentiating outflow tract (OFT). We show that improper specification and proliferation of second heart field (SHF) progenitors in zebrafish Lazarus (lzr) mutants, which lack the transcription factor Pbx4, produces enlarged hearts owkra to an increase in ventricular and smooth muscle cells. Specifically, Pbx4 initially promotes the partitioning of the SHF into anterior progenitors, which contribute to the OFT, and adjacent endothelial cell progenitors, which contribute to posterior pharyngeal arches. Subsequently, Pbx4 limits SHF progenitor (SHFP) proliferation. Single cell RNA sequencing of nkx2.5(+) cells revealed previously unappreciated distinct differentiation states and progenitor subpopulations that normally reside within the SHF and arterial pole of the heart. Specifically, the transcriptional profiles of Pbx4-deficient nkx2.5(+) SHFPs are less distinct and display characteristics of normally discrete proliferative progenitor and anterior, differentiated cardiomyocyte populations. Therefore, our data indicate that the generation of proper OFT size and arch arteries requires Pbx-dependent stratification of unique differentiation states to facilitate both homeotic-like transformations and limit progenitor production within the SHF.
机译：脊椎动物的心脏发育需要时间上明显的分化祖细胞的整合。然而，很少有信号被理解，限制稍后分化的流出道（OFT）的尺寸。我们表明，斑马鱼鳞（LZR）突变体（LZR）突变体中的第二心脏场（SHF）祖细胞的不正确规范和增殖产生扩大的心脏猫蜂鸣，以增加心室和平滑肌细胞。具体地，PBX4最初将SHF的分配促进到前祖细胞中，这有助于OFT和相邻的内皮细胞祖细胞，这有助于咽部曲线曲线。随后，PBX4限制SHF祖（SHFP）增殖。 NKX2.5（+）细胞的单细胞RNA测序揭示了先前未被覆富的不同分化态和祖细胞群，通常存在于心脏的SHF和动脉杆内。具体地，PBX4缺陷NKX2.5（+）SHFP的转录谱不太明显，显示通常离散的增殖性祖细胞和前型分化的心肌细胞群的明显和显示特征。因此，我们的数据表明，适当的尺寸和拱动脉的产生需要独特分化状态的PBX依赖性分层，以促进异形转化并限制SHF内的祖细胞产生。

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