MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts.
BACKGROUND: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pat...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3723828?pdf=render |
| _version_ | 1811228635635384320 |
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| author | Yuxia Yang Wei Ma Dan Wu Yu Huang Hongge Li Junhua Zou Yanju Zhang Meifu Feng Jianyuan Luo |
| author_facet | Yuxia Yang Wei Ma Dan Wu Yu Huang Hongge Li Junhua Zou Yanju Zhang Meifu Feng Jianyuan Luo |
| author_sort | Yuxia Yang |
| collection | DOAJ |
| description | BACKGROUND: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34(+) cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34(+) cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34(+) cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down. CONCLUSION/SIGNIFICANCE: Our data demonstrated that CB CD34(+) cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts. |
| first_indexed | 2024-04-12T10:01:21Z |
| format | Article |
| id | doaj.art-da737c359e474edcb409e84dfc3c38de |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:01:21Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-da737c359e474edcb409e84dfc3c38de2022-12-22T03:37:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7023210.1371/journal.pone.0070232MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts.Yuxia YangWei MaDan WuYu HuangHongge LiJunhua ZouYanju ZhangMeifu FengJianyuan LuoBACKGROUND: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34(+) cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34(+) cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34(+) cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down. CONCLUSION/SIGNIFICANCE: Our data demonstrated that CB CD34(+) cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts.http://europepmc.org/articles/PMC3723828?pdf=render |
| spellingShingle | Yuxia Yang Wei Ma Dan Wu Yu Huang Hongge Li Junhua Zou Yanju Zhang Meifu Feng Jianyuan Luo MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. PLoS ONE |
| title | MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. |
| title_full | MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. |
| title_fullStr | MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. |
| title_full_unstemmed | MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. |
| title_short | MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts. |
| title_sort | mir 17 partly promotes hematopoietic cell expansion through augmenting hif 1α in osteoblasts |
| url | http://europepmc.org/articles/PMC3723828?pdf=render |
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