Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating.
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating.
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DOI：
10.1038/s41598-017-05498-4
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发表时间：
2017-07-12
影响因子：
4.6
通讯作者：
Palis J
中科院分区：
文献类型：
--
作者：
Huang YS;Delgadillo LF;Cyr KH;Kingsley PD;An X;McGrath KE;Mohandas N;Conboy JG;Waugh RE;Wan J;Palis J
造血个体发生的特点是不同的原始和定形红系谱系。成熟的成红细胞在血管外成熟并去核，形成独特的膜骨架，由血影蛋白、4.1R-复合物和抗凝血蛋白R-复合物组分组成，以在成体循环的变迁中存活。然而，对原始成红细胞膜骨架的形成和组成知之甚少，原始成红细胞在胚胎血流中循环时逐渐成熟。我们发现，初级原始成红细胞表达的主要膜骨架基因存在于类似阶段的定形成红细胞，这表明该膜网络的组成和形成是保守的成熟的原始和定形成红细胞，尽管他们各自的血管内和血管外的位置。膜变形性和稳定性的原始成红细胞，测定微流控研究和荧光成像微变形，分别显着增加去核前。这些功能变化与蛋白4.1R同种型转换一致，并且蛋白4.1R无效的原始成红细胞不能建立正常的膜稳定性和变形性。我们的结论是，成熟的原始成红细胞最初导航胚胎血管之前，建立一个可变形的细胞骨架，这是最终形成前去核。红系特异性、蛋白质4.1R依赖性膜骨架的形成不仅是哺乳动物定形红细胞生成的重要特征，也是哺乳动物原始红细胞生成的重要特征。
Hematopoietic ontogeny is characterized by distinct primitive and definitive erythroid lineages. Definitive erythroblasts mature and enucleate extravascularly and form a unique membrane skeleton, composed of spectrin, 4.1R-complex, and ankyrinR-complex components, to survive the vicissitudes of the adult circulation. However, little is known about the formation and composition of the membrane skeleton in primitive erythroblasts, which progressively mature while circulating in the embryonic bloodstream. We found that primary primitive erythroblasts express the major membrane skeleton genes present in similarly staged definitive erythroblasts, suggesting that the composition and formation of this membrane network is conserved in maturing primitive and definitive erythroblasts despite their respective intravascular and extravascular locations. Membrane deformability and stability of primitive erythroblasts, assayed by microfluidic studies and fluorescence imaged microdeformation, respectively, significantly increase prior to enucleation. These functional changes coincide with protein 4.1 R isoform switching and protein 4.1R-null primitive erythroblasts fail to establish normal membrane stability and deformability. We conclude that maturing primitive erythroblasts initially navigate the embryonic vasculature prior to establishing a deformable cytoskeleton, which is ultimately formed prior to enucleation. Formation of an erythroid-specific, protein 4.1R-dependent membrane skeleton is an important feature not only of definitive, but also of primitive, erythropoiesis in mammals.
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DOI：
10.1083/jcb.107.2.413
发表时间：
1988-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lehnert ME;Lodish HF
通讯作者：
Lodish HF
影响因子：
15.9
作者：
CHASIS, JA;COULOMBEL, L;MOHANDAS, N
通讯作者：
MOHANDAS, N
影响因子：
3.6
作者：
KOURY, ST;REPASKY, EA;ECKERT, BS
通讯作者：
ECKERT, BS
影响因子：
20.3
作者：
Isern, Joan;He, Zhiyong;Baron, Margaret H.
通讯作者：
Baron, Margaret H.
影响因子：
20.3
作者：
An, Xiuli;Schulz, Vincent P.;Gallagher, Patrick G.
通讯作者：
Gallagher, Patrick G.