title: miR-221 redirects precursor B cells to the BM and regulates their residence.
abstract: Pluripotent hematopoietic stem cells and multipotent myeloid/lymphoid progenitors express miR-221 and miR-222. When Pax5 expression commits these progenitors to monopotent pre-B lymphocytes the two microRNAs (miRNAs) are downregulated. Upon transplantation, stem cells and progenitors can reside in the BM, while pre-B cells, after their commitment, no longer do so. Retrovirally transduced, doxycycline-induced overexpression of either miR-221 or miR-222 in pre-B-I cells does not revert their monopotency to multipotency. However, upon transplantation miR-221, but not miR-222, transduced pre-B-I cells regain the capacity to reside in the BM. Upon subsequent termination of miR-221-expression by removal of doxycycline, the transplanted cells leave the BM again. Microarray analyses identified 25 downregulated miR-221-target genes, which could function to localize phases of B-lymphocyte development in BM before and after commitment.
authors.affiliation: Research Group Lymphocyte Development, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Knoll
authors.forename: Szandor
authors.initials: S
authors.lastname: Simmons
authors.forename: Corinne
authors.initials: C
authors.lastname: Bouquet
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D015536:Down-Regulation; D004318:Doxycycline; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D054503:Lymphoid Progenitor Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism* / Q000637:transplantation*
chemical_list: D018941:Antigens, CD19; D018398:Homeodomain Proteins; C546122:MIRN221 microRNA, mouse; C546123:MIRN222 microRNA, mouse; D035683:MicroRNAs; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C064658:RAG-1 protein; D004318:Doxycycline
keywords: B cells; Differentiation; MicroRNA-221; Migration; Pax5