Nadine Hätscher, Yonatan Feuermann, Susanne Wingert, Maike Rehage, Frederic Bastian Thalheimer, Christian Weiser, Hanibal Bohnenberger, Klaus Jung, Timm Schroeder, Hubert Serve, Thomas Oellerich, Lothar Hennighausen, Michael A. Rieger
- Haematopoietic stem cells (HSCs) require the right composition of microRNAs (miR) for proper life-long balanced blood regeneration. Here we show a regulatory circuit that prevents excessive HSC self-renewal by upregulation of miR-193b upon self-renewal promoting thrombopoietin (TPO)-MPL-STAT5 signalling. In turn, miR-193b restricts cytokine signalling, by targeting the receptor tyrosine kinase c-KIT. We generated a miR-193b knockout mouse model to unravel the physiological function of miR-193b in haematopoiesis. MiR-193b−/− mice show a selective gradual enrichment of functional HSCs, which are fully competent in multilineage blood reconstitution upon transplantation. The absence of miR-193b causes an accelerated expansion of HSCs, without altering cell cycle or survival, but by decelerating differentiation. Conversely, ectopic miR-193b expression restricts long-term repopulating HSC expansion and blood reconstitution. MiR-193b-deficient haematopoietic stem and progenitor cells exhibit increased basal and cytokine-induced STAT5 and AKT signalling. This STAT5-induced microRNA provides a negative feedback for excessive signalling to restrict uncontrolled HSC expansion.
MetadatenAuthor: | Nadine Hätscher, Yonatan Feuermann, Susanne WingertGND, Maike Rehage, Frederic Bastian ThalheimerORCiDGND, Christian Weiser, Hanibal BohnenbergerORCiD, Klaus Jung, Timm Schroeder, Hubert ServeORCiDGND, Thomas OellerichORCiD, Lothar HennighausenORCiD, Michael A. RiegerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-506030 |
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DOI: | https://doi.org/10.1038/ncomms9928 |
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ISSN: | 2041-1723 |
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Parent Title (English): | Nature Communications |
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Publisher: | Nature Publishing Group UK |
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Place of publication: | [London] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2015 |
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Date of first Publication: | 2015/11/25 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/07/04 |
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Tag: | Cell signalling; Haematopoietic stem cells; Self-renewal; miRNAs |
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Volume: | 6 |
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Issue: | Art. 8928 |
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Page Number: | 11 |
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First Page: | 1 |
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Last Page: | 11 |
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Note: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
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HeBIS-PPN: | 453520499 |
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Institutes: | Medizin / Medizin |
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| Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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