title: Genetic deletion of JAM-C reveals a role in myeloid progenitor generation.
abstract: Hematopoietic stem cells (HSCs) have the capacity to self-renew and continuously differentiate into all blood cell lineages throughout life. At each branching point during differentiation, interactions with the environment are key in the generation of daughter cells with distinct fates. Here, we examined the role of the cell adhesion molecule JAM-C, a protein known to mediate cellular polarity during spermatogenesis, in hematopoiesis. We show that murine JAM-C is highly expressed on HSCs in the bone marrow (BM). Expression correlates with self-renewal, the highest being on long-term repopulating HSCs, and decreases with differentiation, which is maintained longest among myeloid committed progenitors. Inclusion of JAM-C as a sole marker on lineage-negative BM cells yields HSC enrichments and long-term multilineage reconstitution when transferred to lethally irradiated mice. Analysis of Jam-C-deficient mice showed that two-thirds die within 48 hours after birth. In the surviving animals, loss of Jam-C leads to an increase in myeloid progenitors and granulocytes in the BM. Stem cells and myeloid cells from fetal liver are normal in number and homing to the BM. These results provide evidence that JAM-C defines HSCs in the BM and that JAM-C plays a role in controlling myeloid progenitor generation in the BM.
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA, USA. praetor_asja@lilly.com
authors.forename: Asja
authors.initials: A
authors.lastname: Praetor
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: McBride
authors.forename: Henry
authors.initials: H
authors.lastname: Chiu
authors.forename: Linda
authors.initials: L
authors.lastname: Rangell
authors.forename: Lorena
authors.initials: L
authors.lastname: Cabote
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Cupp
authors.forename: Dimitry M
authors.initials: DM
authors.lastname: Danilenko
authors.forename: Sherman
authors.initials: S
authors.lastname: Fong
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D017353:Gene Deletion; D006410:Hematopoiesis / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse