in vivo

Recent publications
Masuda K, Kakugawa K,
Nakayama T, Minato M,
Katsura Y, Kawamoto H. T cell
lineage determination precedes
the initiation of TCRb gene
rearrangement. J. Immunol.
179: 3699-3706, (2007)
Figure 1
Models of lineage commitment during hematopoiesis.
A, Classic dichotomy model. Hematopoietic stem cells (HSC) diverge into CMEP and CLP. Note that CMEP
are sometimes referred to as common myeloid progenitors (CMP). The findings reported by Dr. Weissman’s
group that CLP are present in adult BM has provided support for this model.
B, Myeloid-based model. In this model, the first branch point generates CMEP and CMLP, and the myeloid
potential persists in the T and B cell branches even after these lineages have diverged. This model
postulates that specification towards erythroid, T and B cell lineages proceeds on the basis of a prototypical
myeloid program (Kawamoto H., Trends in Immunol., 2006).
of the thymic microenvironment still remains
obscure. In collaboration with the Unit for Thymic
Environment, we have identified a novel subset of
cortical thymic epithelial cells (cTEC), responsible
for the maintenance of microenvironments in
the thymic cortex of adults (Figure 2). These
cells emerge in the deep thymic cortex, and
eventually replace the entire cortex over time.
Importantly, this cell type has the capacity to
replace damaged cTECs.
Besides the above-mentioned two projects,
we are currently interested in the issue of
whether environmental factors instructively
induce lineage commitment or selectively
support autonomously committed progenitors
during lymphopoiesis. To address this issue, it is
important to establish an experimental system
in which lineage commitment of progenitors
can be monitored with real-time imaging. We
have previously shown that the earliest T cell
progenitors in the thymus retain the potential to
generate NK cells and dendritic cells, and that
the termination of this tri-potentiality with clear
commitment to the T cell lineage occurs before
the initiation of TCRβ chain gene rearrangement.
In order to directly visualize this differentiation
step, we are using GFP transgenic mice in
which the expression of GFP is controlled by the
proximal promoter of the T cell-specific tyrosine
kinase lck.
Our research activities also include the study
of human lympho-hematopoiesis. Cord blood
cells are used as a progenitor source, and the
basic culture system is a modification of the coculture
with murine stromal cells.
Ikawa, T., Kawamoto, H.,
Golodrath A.W., Murre C. E protein
and Notch signaling cooperate to
promote T cell lineage specification
and commitment. J. Exp. Med.
15:1329-1342, (2006)
Kawamoto, H. Close
developmental relationship
between lymphoid and myeloid
lineages. Trends in Immunology.
27: 169-175, (2006)
Masuda K., Kubagawa H., Ikawa T.,
Chen C.C., Kakugawa K., Hattori
M., Kageyama R., Cooper M.D.,
Minato N., Katsura Y., Kawamoto
H. Prethymic T-cell development
defined by the expression of paired
immunoglobulin-like receptors.
EMBO J. 24, 4052-4060 (2005)
Masuda K., Itoi M., Amagai T.,
Minato N., Katsura Y, Kawamoto
H. Thymic anlage is colonized by
progenitors restricted to T, NK and
dendritic cell lineages. J. Immunol.
174: 2525-2532 (2005)
Figure 2 Second generation cTECs emerging postnatally in the deep thymic cortex.
A cryostat section of the thymus from a 7 week old mouse was stained with anti-cytokeratin (K) 5 (green)
and anti-K8 (red) antibodies. Whereas cTECs in the outer cortex are almost exclusively K5 - K8 + (R1), 60
percent of cTECs located between medullary islets in the deep cortex displayed a K5 + K8 + phenotype (R2).
These K5 + K8 + cTECs are thought to represent the second wave cTECs. c: cortex, m: medulla. Bar; 100 mm.
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