TY - JOUR
T1 - Ptk7-deficient mice have decreased hematopoietic stem cell pools as a result of deregulated proliferation and migration
AU - Lhoumeau, Anne Catherine
AU - Arcangeli, Marie Laure
AU - De Grandis, Maria
AU - Giordano, Marilyn
AU - Orsoni, Jean Christophe
AU - Lembo, Frédérique
AU - Bardin, Florence
AU - Marchetto, Sylvie
AU - Aurrand-Lions, Michel
AU - Borg, Jean Paul
N1 - Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/5/15
Y1 - 2016/5/15
N2 - Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling.We showed previously that PTK7, a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis has remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, with the highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss of Ptk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlated with increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling novel and unexpected functions for planar cell polarity pathways in HSC fate.
AB - Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling.We showed previously that PTK7, a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis has remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, with the highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss of Ptk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlated with increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling novel and unexpected functions for planar cell polarity pathways in HSC fate.
UR - http://www.scopus.com/inward/record.url?scp=84975070431&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1500680
DO - 10.4049/jimmunol.1500680
M3 - Article
C2 - 27183644
AN - SCOPUS:84975070431
SN - 0022-1767
VL - 196
SP - 4367
EP - 4377
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -