Common marmoset CD117 + hematopoietic cells possess multipotency

Abstract

Analysis of the hematopoiesis of non-human primates is important to clarify the evolution of primate-specific hematopoiesis and immune regulation. However, the engraftment and development of the primate hematopoietic system are well-documented only in humans and are not clear in non-human primates. Callithrix jacchus (common marmoset, CM) is a New World monkey with a high rate of pregnancy and small size that lives in closed colonies. As stem cell factor (SCF) is an essential molecule for hematopoietic stem cell development in mice and humans, we focused on CD117, the SCF receptor, and examined whether CD117-expressing cells possess the hematopoietic stem/progenitor cell characteristics of newborn marmoset-derived hematopoietic cells that can develop into T cells and B cells. When CD117(+) cell fractions of the bone marrow were transplanted into immunodeficient NOD (non-obese diabetic)/Shi-scid, common γc-null (NOG) mice, these cells engrafted efficiently in the bone marrow and spleens of the NOG mice. The CD117(+) cells developed into myeloid lineage cells, CD20(+) B cells and CD3(+) T cells, which could express CM cytokines in vivo. The development of B cells did not precede that of T cells. The development of CD8(+) T cells was dominant in NOG mice. The engraftment was comparable for both CD117(+)CD34(+) cells and CD117(+)CD34(-) cells. These results suggest that the CD117(+) cell fraction can differentiate into all three cell lineages, and the development of marmoset immunity in the xenogeneic environment follows diverse developmental pathways compared with human immunity.

Para-Nonylphenol Induces Apoptosis of U937 Human Monocyte Leukemia Cells in vitro

“…Even concomitant PI3K and Bcl-2/Bcl-X L inhibition suppresses tumor growth and enhances survival of NOD/SCID-gamma mice in vivo using a U937 cell xenograft model [35]. In immunodeficient NOG mice, xenografted common marmoset CD117 + hematopoietic cells can be differentiated into lymphocytes [36]. Furthermore, many experiments have shown that caspases are activated when apoptosis is induced by other factors, such as the potent antitumor drug doxorubicin [37] and TNF-α [38].…”

Comparative immunity of antigen recognition, differentiation, and other functional molecules: similarities and differences among common marmosets, humans, and mice

“…In parallel with these results, Izawa et al . (2004) [ 29 ] and our group (2008) [ 78 ] observed the multilineage differentiation of CD34+ cells in NOD/SCID and NOG mice. Schrimpf et al .…”

“…Therefore, we established an anti-CM CD34 monoclonal antibody and anti-CM CD117 monoclonal antibody, and identified CD117 as a CM HSC marker using these antibodies [ 29 , 33 ]. Next, we examined if the multipotency and developmental pathway of CM HSCs were similar to those of humans by transplanting the cells into severely immunodeficient NOG mice [ 27 , 55 , 78 ]. CM bone mallow cells were collected from newborn CMs that were abandoned due to a birth of triplets.…”

“…(2) The SRC assay revealed that CD117+ cells developed into T cells and B cells in NOG mice. (3) CD117+ cells developed into mast cells both in vitro and in NOG mice [ 55 , 78 ], (4) CD8 T cells but not B cells predominantly developed after HSC transplantation, and (5) multipotency, evaluated by SRC assay, showed that total engraftment in NOG mice after HSC transplantation was enhanced by CD34 expression. No CD4 T cells were observed in the SRC assay.…”

“…This evidence suggests that the developmental pathways are different between CMs and humans. NOG mice developed not only CM lymphoid cells but also CM myeloid cells, represented by mast cells, early after the transplantation of HSCs into NOG mice [ 78 ]. The CM-transplanted NOG mice expressed the cDNAs of various CM cytokines, suggesting that these CM cells were somewhat functional.…”