TY  - JOUR
A1  - Hätscher, Nadine
A1  - Feuermann, Yonatan
A1  - Wingert, Susanne
A1  - Rehage, Maike
A1  - Thalheimer, Frederic Bastian
A1  - Weiser, Christian
A1  - Bohnenberger, Hanibal
A1  - Jung, Klaus
A1  - Schroeder, Timm
A1  - Serve, Hubert
A1  - Oellerich, Thomas
A1  - Hennighausen, Lothar
A1  - Rieger, Michael A.
T1  - STAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
T2  - Nature Communications
N2  - 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.
KW  - Cell signalling
KW  - Haematopoietic stem cells
KW  - miRNAs
KW  - Self-renewal
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50603
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-506030
SN  - 2041-1723
N1  - 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/
VL  - 6
IS  - Art. 8928
SP  - 1
EP  - 11
PB  - Nature Publishing Group UK
CY  - [London]
ER  -