Open AccessInterleukin-12 supports in vitro self-renewal of long-term hematopoietic stem cells
Author(s) -
Shanshan Zhang,
Mamoru Morita,
Zhao Wang,
Jun Ooehara,
Sen Zhang,
Miner Xie,
Hao Bai,
Wenying Yu,
Xiaofang Wang,
Fang Dong,
Jinhong Wang,
Shihui Ma,
Satoshi Yamazaki,
Hideo Ema
Publication year - 2019
Publication title -
blood science
Language(s) - English
Resource type - Journals
ISSN - 2543-6368
DOI - 10.1097/bs9.0000000000000002
Subject(s) - stem cell factor , haematopoiesis , stem cell , thrombopoietin , microbiology and biotechnology , biology , in vitro , transplantation , immunology , cd34 , cytokine , cell division , cell , medicine , genetics
Hematopoietic stem cells (HSCs) self-renew or differentiate through division. Cytokines are essential for inducing HSC division, but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear. In this study, we compared the effects of interleukin-12 (IL-12) and thrombopoietin (TPO) in combination with stem cell factor (SCF) on in vitro self-renewal of HSCs. Single-cell assays were used to overcome the heterogeneity issue of HSCs, and serum-free conditions were newly established to permit reproduction of data. In single-cell cultures, CD150 + CD48 - CD41 - CD34 - c-Kit + Sca-1 + lineage - HSCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO. Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term (<6 months) HSCs, resulting in a monophasic reconstitution wave formation, whereas IL-12 was more effective than TPO at supporting the in vitro self-renewal of long-term (>6 months) HSCs, resulting in a biphasic reconstitution wave formation. The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.