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In vivo lineage tracing in lymphopoiesis
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Resumo(s)
Lymphocytes are thought to differentiate from a common progenitor, which either
remains in the bone marrow to generate B lymphocytes, or emigrates and, via blood,
seeds the thymus to generate T lymphocytes. Such progenitors were originally termed
common lymphoid progenitors (CLP), and a bone marrow population with both B and
T lymphocyte potential was identified. Although CLP are clearly on their way to feed
into the B lymphocyte lineage, their link to the T lymphocyte lineage in physiology is
less clear. One concern is that CLP were never found in the thymus. Work from
different labs have proposed several bone marrow progenitors as the true progenitors
of T lymphocytes, but the identity of such cells remains elusive. Here, we sought to
address this aspect by in vivo lineage tracing. For that purpose, we analyzed two
mouse lines that expressed Cre recombinase from the interleukin 7 receptor alpha (IL7r) endogenous locus that differed in fluorescent reporter: IL-7riCre Rosa26-YFP
and IL-7riCre Rosa26-tdTomato. In these mice, Cre expression follows the
expression pattern of IL-7r, meaning that it will switch on the reporter to mark IL-7ra
expressing cells, as well as all their progeny. With such tools in hand, we could
determine progenitor-progeny relationships in the lymphocyte lineages. In addition, we
used an inducible model, IL-7riCreERT2 Rosa26-tdTomato, to fine-tune those
relationships at several timepoints after reporter induction. We identified a population
that seems to be the bone marrow progenitor counterpart of the earliest thymic
progenitor. This was validated in adoptive transfer experiments of purified cells into IL7r deficient recipients. Taken together, our data supports the notion that the CLP is a
highly heterogeneous population, and we found a subpopulation within the CLP that is
the bone marrow progenitor that originates the T lymphocyte lineage.
Descrição
Palavras-chave
Lymphocytes Hematopoietic Progenitors Common Lymphoid Progenitor Thymus