title: TIM-family molecules in embryonic hematopoiesis: fetal liver TIM-4(lo) cells have myeloid potential.
abstract: Trans-membrane (or T cell) immunoglobulin and mucin (TIM) molecules are known regulators of immune response whose function in hematopoiesis is unknown. Earlier, we found that tim-1 and tim-4 are expressed by CD45(+) cells in the para-aortic region of chicken embryo. Because the para-aortic region is a known site for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) differentiation and expansion, we hypothesize that TIM molecules have a role in hematopoiesis. To study this role further, we analyzed TIM expression more precisely in chicken para-aortic region and mouse fetal liver hematopoietic cells. Additionally, we examined the hematopoietic potential of TIM-4(+) mouse fetal liver cells with a colony-forming assay. tim-1 gene expression was detected in chicken and mouse embryos in the aorta-gonads-mesonephros-region at the time of HSC emergence, whereas tim-3 mRNA was widely expressed in different tissues. tim-4 expression was restricted to fetal liver CD45(+)F4/80(+) cells. Moreover, two TIM-4(+) populations were distinguished: F4/80(hi)TIM-4(hi) and F4/80(lo)TIM-4(lo). F4/80(hi)TIM-4(hi) cells had no hematopoietic potential and were morphologically similar to mature macrophages, suggesting that they are yolk sac-derived macrophages. Instead, many of the F4/80(lo)TIM-4(lo) cells were c-kit(+) and Sca-1(+) and had primitive morphology and multilineage colony-forming ability. In addition, F4/80(lo)TIM-4(lo) cells included a considerable population expressing ER-MP12, a known marker for macrophage colony-forming cells and other myeloid progenitors. We conclude that TIM molecules are expressed in embryonic hematopoietic tissues in chicken and mouse and that in fetal liver, TIM-4 is expressed by myeloid progenitor cells.
authors: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland; Nordlab Oulu, Oulu University Hospital, Oulu, Finland. Electronic address: riikka.syrjanen@oulu.fi.
authors: Riikka
authors: R
authors: Syrjänen
authors: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland; Nordlab Oulu, Oulu University Hospital, Oulu, Finland.
authors: Petar
authors: P
authors: Petrov
authors: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland.
authors: Virpi
authors: V
authors: Glumoff
authors: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Shentong
authors: S
authors: Fang
authors: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Petri
authors: P
authors: Salven
authors: Nordlab Oulu, Oulu University Hospital, Oulu, Finland; Institute of Diagnostics, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
authors: Eeva-Riitta
authors: ER
authors: Savolainen
authors: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland; Nordlab Oulu, Oulu University Hospital, Oulu, Finland.
authors: Olli
authors: O
authors: Vainio
authors: Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland.
authors: Tatsuya
authors: T
authors: Uchida
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D006413:Hematopoietic System / Q000196:embryology / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D030161:Avian Proteins; D008565:Membrane Proteins; C500399:TIM-4 protein, mouse; C036763:monocyte-macrophage differentiation antigen; D017493:Leukocyte Common Antigens