PTPN13 and β-catenin regulate the quiescence of hematopoietic stem cells and their interaction with the bone marrow niche

Guillermo López-Ruano, Rodrigo Prieto-Bermejo, Teresa L. Ramos, Laura San-Segundo, Luis Ignacio Sánchez-Abarca, Fermín Sánchez-Guijo, José Antonio Pérez-Simón, Jesús Sánchez-Yagüe, Marcial Llanillo, Ángel Hernández-Hernández*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)516-531
Number of pages16
JournalStem Cell Reports
Volume5
Issue number4
DOIs
Publication statusPublished - 13 Oct 2015
Externally publishedYes

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