title: Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.
abstract: To investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lambda5 reporter transgenic mice to Rag1-GFP knockin mice. This allowed us to subfractionate common lymphoid progenitors and pre-pro-B (fraction A) cells into lambda5(-)Rag1(low), lambda5(-)Rag1(high), and lambda5(+)Rag1(high) cells. Clonal in vitro differentiation analysis demonstrated that Rag1(low) cells gave rise to B/T and NK cells. Rag1(high) cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells, whereas the lambda5(+) cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1(high) populations. These cells also expressed a higher level of the surface protein LY6D, providing an additional tool for the analysis of early lymphoid development. These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis.
authors.affiliation: Department for Clinical and Experimental Sciences, Linköping University, Linköping, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Mansson
authors.forename: Sasan
authors.initials: S
authors.lastname: Zandi
authors.forename: Eva
authors.initials: E
authors.lastname: Welinder
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsapogas
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000235:genetics; D015415:Biomarkers; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology; D016131:Lymphocyte Subsets / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D038041:Lymphopoiesis; D051379:Mice; D008822:Mice, Transgenic; D051757:PAX5 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; C489921:Ebf1 protein, mouse; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; C035271:Ly6d protein, mouse; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; C064658:RAG-1 protein