Reprimo基因家族成员reprimo-like（rprml）是胚胎斑马鱼血液发育所必需的。,Scientific Reports

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Reprimo基因家族成员reprimo-like（rprml）是胚胎斑马鱼血液发育所必需的。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-05-09 , DOI: 10.1038/s41598-019-43436-8
Karen Stanic ₁ , German Reig _{2,

3} , Ricardo J Figueroa ₁ , Pedro A Retamal ₁ , Ignacio A Wichmann _{4,

5} , Juan C Opazo ₆ , Gareth I Owen _{1,

4,

7} , Alejandro H Corvalán _{4,

5} , Miguel L Concha _{2,

8} , Julio D Amigo ₁

Affiliation

Reprimo基因家族包含一组单外显子基因，其生理功能仍然知之甚少。迄今，哺乳动物Reprimo（RPRM）已被描述为在G2 / M细胞周期检查点起作用的推定的p53依赖性肿瘤抑制基因。另一个家族成员，类似Reprimo样（RPRML），尚未在生理学或病理学中确立作用。重要的是，RPRML表达模式在斑马鱼和人类物种之间是保守的。在这里，我们使用CRISPR-Cas9和反义吗啉代寡核苷酸，破坏了rprml在斑马鱼中的表达，并证明了其丢失会导致确定性造血功能受损。成血管细胞的形成和造血原始波通常在不存在rprml的情况下发生。在后期开发中，后血岛（PBI）的类红细胞-髓样前体（EMP）显着减少，并且最终的造血干/祖细胞（HSPC）显着下降。此外，rprm1的丢失还会增加尾部造血组织（CHT）内内皮细胞中caspase-3的活性，这是斑马鱼胚胎发育过程中HSPC驻留的第一个血管周围环境。本文中，我们报道了rprm1在斑马鱼胚胎的血管发育过程中，特别是在造血的确定性波浪中的重要作用，首次表明rprm1基因的生理作用。rprml的缺失还会增加尾部造血组织（CHT）内内皮细胞中caspase-3的活性，这是斑马鱼胚胎发育过程中HSPC驻留的第一个血管周围环境。本文中，我们报道了rprm1在斑马鱼胚胎的血管发育过程中，特别是在造血的确定性波浪中的重要作用，首次表明rprm1基因的生理作用。rprml的缺失还会增加尾部造血组织（CHT）内内皮细胞中caspase-3的活性，这是斑马鱼胚胎发育过程中HSPC驻留的第一个血管周围环境。本文中，我们报道了rprm1在斑马鱼胚胎的血管发育过程中，特别是在造血的确定性波浪中的重要作用，首次表明rprm1基因的生理作用。

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The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish.

The Reprimo gene family comprises a group of single-exon genes for which their physiological function remains poorly understood. Heretofore, mammalian Reprimo (RPRM) has been described as a putative p53-dependent tumor suppressor gene that functions at the G2/M cell cycle checkpoint. Another family member, Reprimo-like (RPRML), has not yet an established role in physiology or pathology. Importantly, RPRML expression pattern is conserved between zebrafish and human species. Here, using CRISPR-Cas9 and antisense morpholino oligonucleotides, we disrupt the expression of rprml in zebrafish and demonstrate that its loss leads to impaired definitive hematopoiesis. The formation of hemangioblasts and the primitive wave of hematopoiesis occur normally in absence of rprml. Later in development there is a significant reduction in erythroid-myeloid precursors (EMP) at the posterior blood island (PBI) and a significant decline of definitive hematopoietic stem/progenitor cells (HSPCs). Furthermore, loss of rprml also increases the activity of caspase-3 in endothelial cells within the caudal hematopoietic tissue (CHT), the first perivascular niche where HSPCs reside during zebrafish embryonic development. Herein, we report an essential role for rprml during hematovascular development in zebrafish embryos, specifically during the definitive waves of hematopoiesis, indicating for the first time a physiological role for the rprml gene.

更新日期：2019-05-16

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