PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche

Stem Cell Reports
Guillermo López-RuanoÁngel Hernández-Hernández

Abstract

The regulation of hematopoietic stem cells (HSCs) depends on the integration of the multiple signals received from the bone marrow niche. We show the relevance of the protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control HSCs adhesiveness, cell cycling, and quiescence. Lethally irradiated mice transplanted with Lin(-) bone marrow cells in which PTPN13 or β-catenin had been silenced showed a significant increase of long-term (LT) and short-term (ST) HSCs. A decrease in cycling cells was also found, together with an increase in quiescence. The decreased expression of PTPN13 or β-catenin was linked to the upregulation of several genes coding for integrins and several cadherins, explaining the higher cell adhesiveness. Our data are consistent with the notion that the levels of PTPN13 and β-catenin must be strictly regulated by extracellular signaling to regulate HSC attachment to the niche and the balance between proliferation and quiescence.

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Citations

Apr 14, 2016·Current Opinion in Hematology·Madhav Seshadri, Cheng-Kui Qu
Jun 26, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yifan ZhaoYubin Zhang
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Nov 25, 2018·The Journal of Experimental Medicine·Yael RazNeta Erez
Jun 27, 2018·Journal of Experimental & Clinical Cancer Research : CR·Rodrigo Prieto-BermejoÁngel Hernández-Hernández
Feb 16, 2019·Journal of Experimental & Clinical Cancer Research : CR·Alejandro Pérez-FernándezÁngel Hernández-Hernández
Jan 11, 2020·Haematologica·Rodrigo Prieto-BermejoÁngel Hernández-Hernández
Dec 17, 2020·Biomolecules·Soha McheikGilles Freiss

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorting
FACS
flow cytometry
transfection

Software Mentioned

Infinicyt
FACS Flowing

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