Loss of CD44dimExpression from Early Progenitor Cells Marks T-Cell Lineage Commitment in the Human Thymus.
Human T-cell development is less well studied than its murine counterpart due to the lack of genetic tools and the difficulty of obtaining cells and tissues. Here, we report the transcriptional landscape of 11 immature, consecutive human T-cell developmental stages. The changes in gene expression of cultured stem cells on OP9-DL1 match those ofex vivoisolated murine and human thymocytes. These analyses led us to define evolutionary conserved gene signatures that represent pre- and post-αβ T-cell commitment stages. We found that loss of dim expression of CD44 marks human T-cell commitment in early CD7+CD5+CD45dimcells, before the acquisition of CD1a surface expression. The CD44-CD1a-post-committed thymocytes have initiated in frame T-cell receptor rearrangements that are accompanied by loss of capacity to differentiate toward myeloid, B- and NK-lineages, unlike uncommitted CD44dimCD1a-thymocytes. Therefore, loss of CD44 represents a previously unrecognized human thymocyte stage that defines the earliest committed T-cell population in the thymus.
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
Kirsten
K
Canté-Barrett
Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital , Rotterdam , Netherlands.
Rui D
RD
Mendes
Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital , Rotterdam , Netherlands.
Yunlei
Y
Li
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
Eric
E
Vroegindeweij
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden , Netherlands.
Karin
K
Pike-Overzet
Department of Immunology, Erasmus Medical Center , Rotterdam , Netherlands.
Tamara
T
Wabeke
Department of Immunology, Erasmus Medical Center , Rotterdam , Netherlands.
Anton W
AW
Langerak
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
Rob
R
Pieters
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden , Netherlands.
Frank J T
FJ
Staal
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
Jules P P
JP
Meijerink
CD44; OP9-DL1; T-cell commitment; gene expression; human T-cell development; multi-lineage potential; thymus