Bmi1 confers resistance to oxidative stress on hematopoietic stem cells.
The polycomb-group (PcG) proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression of Bmi1, a gene encoding a core component of polycomb repressive complex (PRC) 1, maintained self-renewing hematopoietic stem cells (HSCs) during long-term c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3350495?pdf=render |
| _version_ | 1811319627322490880 |
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| author | Shunsuke Nakamura Motohiko Oshima Jin Yuan Atsunori Saraya Satoru Miyagi Takaaki Konuma Satoshi Yamazaki Mitsujiro Osawa Hiromitsu Nakauchi Haruhiko Koseki Atsushi Iwama |
| author_facet | Shunsuke Nakamura Motohiko Oshima Jin Yuan Atsunori Saraya Satoru Miyagi Takaaki Konuma Satoshi Yamazaki Mitsujiro Osawa Hiromitsu Nakauchi Haruhiko Koseki Atsushi Iwama |
| author_sort | Shunsuke Nakamura |
| collection | DOAJ |
| description | The polycomb-group (PcG) proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression of Bmi1, a gene encoding a core component of polycomb repressive complex (PRC) 1, maintained self-renewing hematopoietic stem cells (HSCs) during long-term culture. However, the effects of overexpression of Bmi1 on HSCs in vivo remained to be precisely addressed.In this study, we generated a mouse line where Bmi1 can be conditionally overexpressed under the control of the endogenous Rosa26 promoter in a hematopoietic cell-specific fashion (Tie2-Cre;R26Stop(FL)Bmi1). Although overexpression of Bmi1 did not significantly affect steady state hematopoiesis, it promoted expansion of functional HSCs during ex vivo culture and efficiently protected HSCs against loss of self-renewal capacity during serial transplantation. Overexpression of Bmi1 had no effect on DNA damage response triggered by ionizing radiation. In contrast, Tie2-Cre;R26Stop(FL)Bmi1 HSCs under oxidative stress maintained a multipotent state and generally tolerated oxidative stress better than the control. Unexpectedly, overexpression of Bmi1 had no impact on the level of intracellular reactive oxygen species (ROS).Our findings demonstrate that overexpression of Bmi1 confers resistance to stresses, particularly oxidative stress, onto HSCs. This thereby enhances their regenerative capacity and suggests that Bmi1 is located downstream of ROS signaling and negatively regulated by it. |
| first_indexed | 2024-04-13T12:46:10Z |
| format | Article |
| id | doaj.art-093d1ae3ccf94c2f833142f2f673e03e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T12:46:10Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-093d1ae3ccf94c2f833142f2f673e03e2022-12-22T02:46:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3620910.1371/journal.pone.0036209Bmi1 confers resistance to oxidative stress on hematopoietic stem cells.Shunsuke NakamuraMotohiko OshimaJin YuanAtsunori SarayaSatoru MiyagiTakaaki KonumaSatoshi YamazakiMitsujiro OsawaHiromitsu NakauchiHaruhiko KosekiAtsushi IwamaThe polycomb-group (PcG) proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression of Bmi1, a gene encoding a core component of polycomb repressive complex (PRC) 1, maintained self-renewing hematopoietic stem cells (HSCs) during long-term culture. However, the effects of overexpression of Bmi1 on HSCs in vivo remained to be precisely addressed.In this study, we generated a mouse line where Bmi1 can be conditionally overexpressed under the control of the endogenous Rosa26 promoter in a hematopoietic cell-specific fashion (Tie2-Cre;R26Stop(FL)Bmi1). Although overexpression of Bmi1 did not significantly affect steady state hematopoiesis, it promoted expansion of functional HSCs during ex vivo culture and efficiently protected HSCs against loss of self-renewal capacity during serial transplantation. Overexpression of Bmi1 had no effect on DNA damage response triggered by ionizing radiation. In contrast, Tie2-Cre;R26Stop(FL)Bmi1 HSCs under oxidative stress maintained a multipotent state and generally tolerated oxidative stress better than the control. Unexpectedly, overexpression of Bmi1 had no impact on the level of intracellular reactive oxygen species (ROS).Our findings demonstrate that overexpression of Bmi1 confers resistance to stresses, particularly oxidative stress, onto HSCs. This thereby enhances their regenerative capacity and suggests that Bmi1 is located downstream of ROS signaling and negatively regulated by it.http://europepmc.org/articles/PMC3350495?pdf=render |
| spellingShingle | Shunsuke Nakamura Motohiko Oshima Jin Yuan Atsunori Saraya Satoru Miyagi Takaaki Konuma Satoshi Yamazaki Mitsujiro Osawa Hiromitsu Nakauchi Haruhiko Koseki Atsushi Iwama Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. PLoS ONE |
| title | Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. |
| title_full | Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. |
| title_fullStr | Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. |
| title_full_unstemmed | Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. |
| title_short | Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. |
| title_sort | bmi1 confers resistance to oxidative stress on hematopoietic stem cells |
| url | http://europepmc.org/articles/PMC3350495?pdf=render |
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