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Cyclin A2 regulates erythrocyte morphology and numbers

Jayapal, Senthil Raja ; Ang, Heather Yin Kuan ; Wang, Chelsia Qiuxia ; Bisteau, Xavier ; Caldez, Matias J. ; Xuan, Gan Xiao ; Yu, Weimiao ; Tergaonkar, Vinay ; Osato, Motomi and Lim, Bing , et al. (2016) In Cell Cycle 15(22). p.3070-3081
Abstract

Cyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid-specific cyclin A2 knockout mice are viable but displayed increased mean erythrocyte volume and reduced erythrocyte counts, as well as increased frequency of erythrocytes containing Howell-Jolly bodies. Erythroblasts lacking cyclin A2 displayed defective enucleation, resulting in reduced production of enucleated erythrocytes and increased frequencies of erythrocytes... (More)

Cyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid-specific cyclin A2 knockout mice are viable but displayed increased mean erythrocyte volume and reduced erythrocyte counts, as well as increased frequency of erythrocytes containing Howell-Jolly bodies. Erythroblasts lacking cyclin A2 displayed defective enucleation, resulting in reduced production of enucleated erythrocytes and increased frequencies of erythrocytes containing nuclear remnants. Deletion of the Cdk inhibitor p27Kip1 but not Cdk2, ameliorated the erythroid defects resulting from deficiency of cyclin A2, confirming the critical role of cyclin A2/Cdk activity in erythroid development. Loss of cyclin A2 in bone marrow cells in semisolid culture prevented the formation of BFU-E but not CFU-E colonies, uncovering its essential role in BFU-E function. Our data unveils the critical functions of cyclin A2 in regulating mammalian erythropoiesis.

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publication status
published
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keywords
Animal models, BFU-E colonies, CFU-E colonies, Cyclin A2, Cyclins, DNA damage and repair, enucleation, erythropoiesis, G1/S transition, Hematopoiesis, Howell-Jolly bodies, Protein kinases, Stem cells
in
Cell Cycle
volume
15
issue
22
pages
12 pages
publisher
Landes Bioscience
external identifiers
  • scopus:84991035715
  • pmid:27657745
ISSN
1538-4101
DOI
10.1080/15384101.2016.1234546
language
English
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no
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18eeb23b-6ff9-4de8-b909-714bdbb7356f
date added to LUP
2019-09-18 13:46:16
date last changed
2019-11-25 09:34:35
@article{18eeb23b-6ff9-4de8-b909-714bdbb7356f,
  abstract     = {<p>Cyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid-specific cyclin A2 knockout mice are viable but displayed increased mean erythrocyte volume and reduced erythrocyte counts, as well as increased frequency of erythrocytes containing Howell-Jolly bodies. Erythroblasts lacking cyclin A2 displayed defective enucleation, resulting in reduced production of enucleated erythrocytes and increased frequencies of erythrocytes containing nuclear remnants. Deletion of the Cdk inhibitor p27<sup>Kip1</sup> but not Cdk2, ameliorated the erythroid defects resulting from deficiency of cyclin A2, confirming the critical role of cyclin A2/Cdk activity in erythroid development. Loss of cyclin A2 in bone marrow cells in semisolid culture prevented the formation of BFU-E but not CFU-E colonies, uncovering its essential role in BFU-E function. Our data unveils the critical functions of cyclin A2 in regulating mammalian erythropoiesis.</p>},
  author       = {Jayapal, Senthil Raja and Ang, Heather Yin Kuan and Wang, Chelsia Qiuxia and Bisteau, Xavier and Caldez, Matias J. and Xuan, Gan Xiao and Yu, Weimiao and Tergaonkar, Vinay and Osato, Motomi and Lim, Bing and Kaldis, Philipp},
  issn         = {1538-4101},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {3070--3081},
  publisher    = {Landes Bioscience},
  series       = {Cell Cycle},
  title        = {Cyclin A2 regulates erythrocyte morphology and numbers},
  url          = {http://dx.doi.org/10.1080/15384101.2016.1234546},
  doi          = {10.1080/15384101.2016.1234546},
  volume       = {15},
  year         = {2016},
}