Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene.
A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4(lo)CD8(-)CD25(-)CD44(+)c-Kit(+) cells that expressed elevated levels of Notch-1 mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19(-), B220(+), Thy1(+) and CD4(+) cells. Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off.
Gounari
Fotini
F
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Aifantis
Iannis
I
Martin
Colin
C
Fehling
Hans-Joerg
HJ
Hoeflinger
Sonja
S
Leder
Philip
P
von Boehmer
Harald
H
Reizis
Boris
B
D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells; D014157:Transcription Factors
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; C090377:pre-T cell receptor alpha