OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo
Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic nic...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506115001129 |
| _version_ | 1818547764197326848 |
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| author | Xiaoli Chen Qianhao Zhao Chen Li Yang Geng Ke Huang Jian Zhang Xiaoshan Wang Jiaqi Yang Tongjie Wang Chengxiang Xia Xiaofei Liu Minghui Meng Dan Yang Yi Zheng Juan Du Xiangzhong Zhang Jiekai Chen Guangjin Pan Jinyong Wang |
| author_facet | Xiaoli Chen Qianhao Zhao Chen Li Yang Geng Ke Huang Jian Zhang Xiaoshan Wang Jiaqi Yang Tongjie Wang Chengxiang Xia Xiaofei Liu Minghui Meng Dan Yang Yi Zheng Juan Du Xiangzhong Zhang Jiekai Chen Guangjin Pan Jinyong Wang |
| author_sort | Xiaoli Chen |
| collection | DOAJ |
| description | Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo. |
| first_indexed | 2024-12-12T08:11:02Z |
| format | Article |
| id | doaj.art-4492fe1621b54b62b2aace7752943b04 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-12T08:11:02Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-4492fe1621b54b62b2aace7752943b042022-12-22T00:31:47ZengElsevierStem Cell Research1873-50611876-77532015-09-0115239540210.1016/j.scr.2015.08.009OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivoXiaoli Chen0Qianhao Zhao1Chen Li2Yang Geng3Ke Huang4Jian Zhang5Xiaoshan Wang6Jiaqi Yang7Tongjie Wang8Chengxiang Xia9Xiaofei Liu10Minghui Meng11Dan Yang12Yi Zheng13Juan Du14Xiangzhong Zhang15Jiekai Chen16Guangjin Pan17Jinyong Wang18Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Hematology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaFlow Core facility, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Hematology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGenerating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.http://www.sciencedirect.com/science/article/pii/S1873506115001129Hematopoietic progenitorsPluripotent stem cellsOP9TeratomaLhx2 |
| spellingShingle | Xiaoli Chen Qianhao Zhao Chen Li Yang Geng Ke Huang Jian Zhang Xiaoshan Wang Jiaqi Yang Tongjie Wang Chengxiang Xia Xiaofei Liu Minghui Meng Dan Yang Yi Zheng Juan Du Xiangzhong Zhang Jiekai Chen Guangjin Pan Jinyong Wang OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo Stem Cell Research Hematopoietic progenitors Pluripotent stem cells OP9 Teratoma Lhx2 |
| title | OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| title_full | OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| title_fullStr | OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| title_full_unstemmed | OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| title_short | OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| title_sort | op9 lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo |
| topic | Hematopoietic progenitors Pluripotent stem cells OP9 Teratoma Lhx2 |
| url | http://www.sciencedirect.com/science/article/pii/S1873506115001129 |
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