TY - JOUR
T1 - Paracrine CCL17 and CCL22 signaling regulates hematopoietic stem/progenitor cell migration and retention in mouse fetal liver
AU - Konno, Katsuhiro
AU - Sasaki, Tatsuya
AU - Kulkeaw, Kasem
AU - Sugiyama, Daisuke
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Exploratory Research from the Project for Realization of Regenerative Medicine of the Ministry of Education, Culture, Sports, Science and Technology ; and by a bilateral exchange grant between Germany and Japan of the Japan Society for the Promotion of Science . We thank Drs. Keai Sinn Tan and Yumine Ayako for support and helpful discussion, Mis. Kaneyuki Ayako and Hirowatari Aiko for support and Dr. Elise Lamar for critical reading of our manuscript.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6/30
Y1 - 2020/6/30
N2 - Fetal liver (FL) is the major embryonic hematopoietic organ and a site where circulating hematopoietic stem/progenitor cells (HSPCs) reside. However, HSPC migration/retention mechanisms in FL remain unclear. A chemokine screen revealed that the CCR4 ligands CCL17 and CCL22 are highly expressed in mouse embryonic day (E) 12.5 FL. Flow cytometric analysis confirmed CCR4 expression in FL HSPCs. To identify sources of CCL17 and CCL22, we fractionated FL into various cell types and found that Ccl17 and Ccl22 were predominantly expressed in HPCs/matured HCs. In vitro cell migration analysis confirmed enhanced HSPC migration in the presence of HPCs/matured HCs. Furthermore, exo-utero injection of anti-CCR4 neutralizing antibody into pregnant mice significantly reduced the number of FL HSPCs in embryos. These data demonstrate a paracrine mechanism by which HSPC migration/retention is regulated by CCL17 and CCL22 secreted from HPCs or matured HCs in FL.
AB - Fetal liver (FL) is the major embryonic hematopoietic organ and a site where circulating hematopoietic stem/progenitor cells (HSPCs) reside. However, HSPC migration/retention mechanisms in FL remain unclear. A chemokine screen revealed that the CCR4 ligands CCL17 and CCL22 are highly expressed in mouse embryonic day (E) 12.5 FL. Flow cytometric analysis confirmed CCR4 expression in FL HSPCs. To identify sources of CCL17 and CCL22, we fractionated FL into various cell types and found that Ccl17 and Ccl22 were predominantly expressed in HPCs/matured HCs. In vitro cell migration analysis confirmed enhanced HSPC migration in the presence of HPCs/matured HCs. Furthermore, exo-utero injection of anti-CCR4 neutralizing antibody into pregnant mice significantly reduced the number of FL HSPCs in embryos. These data demonstrate a paracrine mechanism by which HSPC migration/retention is regulated by CCL17 and CCL22 secreted from HPCs or matured HCs in FL.
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U2 - 10.1016/j.bbrc.2020.04.045
DO - 10.1016/j.bbrc.2020.04.045
M3 - Article
C2 - 32439173
AN - SCOPUS:85084745538
SN - 0006-291X
VL - 527
SP - 730
EP - 736
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -