Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.
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.
Mansson
Robert
R
Department for Clinical and Experimental Sciences, Linköping University, Linköping, Sweden.
Zandi
Sasan
S
Welinder
Eva
E
Tsapogas
Panagiotis
P
Sakaguchi
Nobuo
N
Bryder
David
D
Sigvardsson
Mikael
M
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
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