in vivo

Laboratory for
Lymphocyte Development
During hematopoiesis, pluripotent
hematopoietic stem cells (HSC) become
sequentially restricted in their developmental
potential to give rise to a variety of lineagecommitted
progenitors. The major aim of the
Laboratory for Lymphocyte Development is to
elucidate the molecular mechanisms that regulate
cell fate decisions in the process of lineage
restriction from HSC to unipotent progenitors.
We have previously established a clonal assay
system that makes it possible to examine the
developmental potential of individual progenitor
cells toward T, B and myeloid cell lineages. This
work has led to a fundamental redefinition of the
nature of lymphoid progenitors and the ontogeny
and phylogeny of T- and B-cell development.
Process of lineage commitment in
hematopoiesis
Team leader
Hiroshi Kawamoto
Research Scientists : Tomokatsu Ikawa
Kiyokazu Kakugawa
Technical Staff : Rumi Satoh
Student Trainee : Yuuki Hayashi
Assistant
: Misa Uenoyama
Visiting Scientists : Nagahiro Minato
Yoshimoto Katsura
The classic dichotomy model of
hematopoiesis postulates that the first step
of differentiation from the HSC generates
the common myelo-erythroid and common
lymphoid progenitors (CLP) (Figure 1A). Our
previous studies in fetal mice, however,
indicated that the first step of lineage restriction
of HSC is the generation of myelo-lymphoid
lineage progenitors and myelo-erythroid lineage
progenitors (Figure 1B). Most notably , the myeloid
potential is retained even after the segregation
of myelo-lymphoid progenitor towards T and B
cell lineages. Thus, each process of specification
towards T, B and erythroid lineages appears to
proceed accompanying the prototypical myeloid
program. Recently we have termed this model
the “myeloid-based model”. The concept of
the CLP has, however, persisted in models
of adult hematopoiesis, since several groups
have provided experimental results supporting
the presence of CLP in the bone marrow.
We have been analyzing the developmental
potential of progenitors in adult mice, and have
recently obtained evidence indicating that the
myeloid-based model is also applicable to adult
hematopoiesis (Wada et al, Nature, 2008).
Progenitors for thymic epithelial cells in
adult thymus
We are also interested in the development
of thymic epithelial cells, and are now focusing
on the homeostasis of thymic epithelial cells
in adult mice. Although the early steps in the
generation of thymic epithelial cells have recently
been documented, the postnatal development
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