title: Clonal allelic predetermination of immunoglobulin-κ rearrangement.
abstract: Although most genes are expressed biallelically, a number of key genomic sites--including immune and olfactory receptor regions--are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue. Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-κ (Igκ) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells. This is accompanied at the molecular level by underlying allelic changes in asynchronous replication timing patterns at the κ locus. These experiments may serve to define a new concept of stem cell plasticity.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, POB 12272, Ein Kerem, Jerusalem 91120, Israel.
authors.forename: Marganit
authors.initials: M
authors.lastname: Farago
authors.forename: Chaggai
authors.initials: C
authors.lastname: Rosenbluh
authors.forename: Maya
authors.initials: M
authors.lastname: Tevlin
authors.forename: Shira
authors.initials: S
authors.lastname: Fraenkel
authors.forename: Sharon
authors.initials: S
authors.lastname: Schlesinger
authors.forename: Hagit
authors.initials: H
authors.lastname: Masika
authors.forename: Masha
authors.initials: M
authors.lastname: Gouzman
authors.forename: Grace
authors.initials: G
authors.lastname: Teng
authors.forename: David
authors.initials: D
authors.lastname: Schatz
authors.forename: Yoach
authors.initials: Y
authors.lastname: Rais
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Hanna
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mostoslavsky
authors.forename: Howard
authors.initials: H
authors.lastname: Cedar
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Bergman
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D042522:DNA Replication Timing; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics*; D006410:Hematopoiesis; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018448:Models, Immunological; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013269:Stochastic Processes
chemical_list: D007145:Immunoglobulin kappa-Chains