Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis
Autophagy is an effective strategy for cell development by recycling cytoplasmic constituents. Genetic deletion of autophagy mediator Atg7 in hematopoietic stem cells (HSCs) can lead to failure of megakaryopoiesis and enhanced autophagy has been implicated in various hematological disorders such as...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2016.1204436 |
| _version_ | 1797684364023169024 |
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| author | Qi Wang Tao You Hongqiong Fan Yinyan Wang Tinatian Chu Mortimer Poncz Li Zhu |
| author_facet | Qi Wang Tao You Hongqiong Fan Yinyan Wang Tinatian Chu Mortimer Poncz Li Zhu |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | Autophagy is an effective strategy for cell development by recycling cytoplasmic constituents. Genetic deletion of autophagy mediator Atg7 in hematopoietic stem cells (HSCs) can lead to failure of megakaryopoiesis and enhanced autophagy has been implicated in various hematological disorders such as immune thrombocytopenia and myelodysplastic syndrome. Here, we examined the hypothesis that optimal autophagy is essential for megakaryopoiesis and thrombopoiesis by altering autophagy using pharmacological approaches. When autophagy was induced by rapamycin or inhibited by bafilomycin A1 in fetal liver cells, we observed a significant decrease in high ploidy megakaryocytes, a reduction of CD41 and CD61 co-expressing cells, and less proplatelet or platelet formation. Additionally, reduced cell size was shown in megakaryocytes derived from rapamycin, but not bafilomycin A1-treated mouse fetal liver cells. However, when autophagy was altered in mature megakaryocytes, we observed no significant change in proplatelet formation, which was consistent with normal platelet counts, megakaryocyte numbers, and ploidy in Atg7flox/flox PF4-Cre mice with megakaryocyte- and platelet-specific deletion of autophagy-related gene Atg7. Therefore, our findings suggest that either induction or inhibition of autophagy in the early stage of megakaryopoiesis suppresses megakaryopoiesis and thrombopoiesis. |
| first_indexed | 2024-03-12T00:28:38Z |
| format | Article |
| id | doaj.art-ddef8eb04f3c4568b8e1ff5ebe259784 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:28:38Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-ddef8eb04f3c4568b8e1ff5ebe2597842023-09-15T10:26:28ZengTaylor & Francis GroupPlatelets0953-71041369-16352017-01-01281828910.1080/09537104.2016.12044361204436Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesisQi Wang0Tao You1Hongqiong Fan2Yinyan Wang3Tinatian Chu4Mortimer Poncz5Li Zhu6Soochow UniversitySoochow UniversitySoochow UniversitySoochow UniversitySoochow UniversityPerelman School of Medicine at the University of PennsylvaniaSoochow UniversityAutophagy is an effective strategy for cell development by recycling cytoplasmic constituents. Genetic deletion of autophagy mediator Atg7 in hematopoietic stem cells (HSCs) can lead to failure of megakaryopoiesis and enhanced autophagy has been implicated in various hematological disorders such as immune thrombocytopenia and myelodysplastic syndrome. Here, we examined the hypothesis that optimal autophagy is essential for megakaryopoiesis and thrombopoiesis by altering autophagy using pharmacological approaches. When autophagy was induced by rapamycin or inhibited by bafilomycin A1 in fetal liver cells, we observed a significant decrease in high ploidy megakaryocytes, a reduction of CD41 and CD61 co-expressing cells, and less proplatelet or platelet formation. Additionally, reduced cell size was shown in megakaryocytes derived from rapamycin, but not bafilomycin A1-treated mouse fetal liver cells. However, when autophagy was altered in mature megakaryocytes, we observed no significant change in proplatelet formation, which was consistent with normal platelet counts, megakaryocyte numbers, and ploidy in Atg7flox/flox PF4-Cre mice with megakaryocyte- and platelet-specific deletion of autophagy-related gene Atg7. Therefore, our findings suggest that either induction or inhibition of autophagy in the early stage of megakaryopoiesis suppresses megakaryopoiesis and thrombopoiesis.http://dx.doi.org/10.1080/09537104.2016.1204436autophagymegakaryopoiesisthrombopoiesis |
| spellingShingle | Qi Wang Tao You Hongqiong Fan Yinyan Wang Tinatian Chu Mortimer Poncz Li Zhu Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis Platelets autophagy megakaryopoiesis thrombopoiesis |
| title | Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis |
| title_full | Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis |
| title_fullStr | Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis |
| title_full_unstemmed | Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis |
| title_short | Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis |
| title_sort | rapamycin and bafilomycin a1 alter autophagy and megakaryopoiesis |
| topic | autophagy megakaryopoiesis thrombopoiesis |
| url | http://dx.doi.org/10.1080/09537104.2016.1204436 |
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