Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating
Abstract 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 vicissitude...
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2017
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oai:doaj.org-article:59ae1bf1686e4ba7bff3a96a98431c782021-12-02T16:06:17ZCirculating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating10.1038/s41598-017-05498-42045-2322https://doaj.org/article/59ae1bf1686e4ba7bff3a96a98431c782017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05498-4https://doaj.org/toc/2045-2322Abstract 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.Yu-Shan HuangLuis F. DelgadilloKathryn H. CyrPaul D. KingsleyXiuli AnKathleen E. McGrathNarla MohandasJohn G. ConboyRichard E. WaughJiandi WanJames PalisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Yu-Shan Huang Luis F. Delgadillo Kathryn H. Cyr Paul D. Kingsley Xiuli An Kathleen E. McGrath Narla Mohandas John G. Conboy Richard E. Waugh Jiandi Wan James Palis Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
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Abstract 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. |
format |
article |
author |
Yu-Shan Huang Luis F. Delgadillo Kathryn H. Cyr Paul D. Kingsley Xiuli An Kathleen E. McGrath Narla Mohandas John G. Conboy Richard E. Waugh Jiandi Wan James Palis |
author_facet |
Yu-Shan Huang Luis F. Delgadillo Kathryn H. Cyr Paul D. Kingsley Xiuli An Kathleen E. McGrath Narla Mohandas John G. Conboy Richard E. Waugh Jiandi Wan James Palis |
author_sort |
Yu-Shan Huang |
title |
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
title_short |
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
title_full |
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
title_fullStr |
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
title_full_unstemmed |
Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating |
title_sort |
circulating primitive erythroblasts establish a functional, protein 4.1r-dependent cytoskeletal network prior to enucleating |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/59ae1bf1686e4ba7bff3a96a98431c78 |
work_keys_str_mv |
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