title: Chemokine polyreactivity of IL7Rα+CSF-1R+ lympho-myeloid progenitors in the developing fetal liver.
abstract: In murine ontogeny, fetal liver is the major hemato- and B-lymphopoietic site until birth. Hematopoiesis develops in largely non-hematopoietic niches, which provide contacts, chemokines and cytokines that induce migration, residence, proliferation and differentiation of progenitors. Within early multipotent progenitors an IL7Rα(+)CSF-1R(+) subset expressed a mixture of lymphoid- and myeloid-specific genes and differentiated to lymphoid and myeloid lineages in vitro. By contrast, IL7Rα(+) cells were lymphoid-committed, and CSF-1R(+) cells were erythro-myeloid-restricted. To respond to a multitude of chemokines single biphenotypic cells expressed CXCR4 and as many as five other chemokine receptors. The monopotent IL7Rα(+) and CSF-1R(+)progenitors all expressed CXCR4, and mutually exclusive, more restricted sets of the analysed five chemokine receptors. This study proposes that chemokine polyreactive, cytokine-bipotent and monopotent progenitors transmigrate through LYVE-1(high) endothelium, attracted by selected chemokines, and reach the IL7- and CSF-1-producing ALCAM(high) mesenchymal niche, attracted by other sets of chemokines, to differentiate to B-lymphoid respectively myeloid cells.
authors.affiliation: Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kajikhina
authors.affiliation: Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
authors.affiliation: Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsuneto
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D054377:Chemokine CXCL12 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D018925:Chemokines; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D019707:Receptors, Chemokine; D020395:Receptors, Interleukin-7; D014157:Transcription Factors; C415350:interleukin-7 receptor, alpha chain; D016186:Receptor, Macrophage Colony-Stimulating Factor