PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche.
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.
Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Guillermo
G
López-Ruano
Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Rodrigo
R
Prieto-Bermejo
IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Teresa L
TL
Ramos
IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Laura
L
San-Segundo
Department of Hematology, Hospital Universitario Virgen del Rocío/IBIS/CSIC/University of Seville, Seville 41013, Spain.
Luis Ignacio
LI
Sánchez-Abarca
IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Fermín
F
Sánchez-Guijo
Department of Hematology, Hospital Universitario Virgen del Rocío/IBIS/CSIC/University of Seville, Seville 41013, Spain.
José Antonio
JA
Pérez-Simón
Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Jesús
J
Sánchez-Yagüe
Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Marcial
M
Llanillo
Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain. Electronic address: angelhh@usal.es.
Ángel
Á
Hernández-Hernández
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D055153:Stem Cell Niche; D034061:Thrombopoiesis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D051176:beta Catenin; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; C516743:Ptpn13 protein, mouse