Generation of hematopoietic stem cells,
in the mouse embryo. (A. Cumano).
Hematopoietic stem cells (HSC) guaranty the production of blood
cells throughout life. HSC are not generated in the hematopoietic
organs but are produced exogenously.
The dorsal aorta develops from the intra-embryonic mesoderm, called
the Splanchnopleura (Sp), the anlage of the mesonephros, mesentery,
and gonads develop in this site after the 10th day of gestation
and this region is then called AGM (Aorta, Gonads, Mesonephros).
We have previously established that the HSC are generated from hematopoietic
precursors in the intra-embryonic mesoderm are the only ones capable
of long-term reconstitution of the hematopoietic compartment of
adult NK-deficient hosts. They can thus be called HSC. The yolk
sac-derived (YS) precursors are unable of long-term engraftment
of recipient mice. We identified surface markers that allowed the
isolation of a population of multipotent hematopoietic precursors,
in the AGM, represented at a frequency of one in three cells. We
sorted these precursors and analyzed the pattern of expression of
genes involved in hematopoietic differentiation. This analysis allowed
us to postulate that HSC are generated in the sub-aortic mesenchymal
patches. This population is already at this stage strictly engaged
in hematiopoietic fate and is unable to give rise to neural precursors.
We identified a pipulation of primitive macrophages in the YS and
AGM and we are actively pursuing the characterization of the origin
and function of these cells.
B cell development in the absence of
interleukin 7. (P. Vieira and A. Cumano).
In the absence of interleukin 7 (IL-7), the numbers of T and B lymphocytes
are ten fold reduced in the peripheral lymphoid organs. Our analysis
showed that B lymphopoiesis is completely abrogated in the bone
marrow of adult IL-7-/- mice starting at the 7th week of age, illustrating
the essential role of IL-7 in bone marrow lymphopoiesis. We showed
that the majority of B lymphocytes in these mice were of fetal or
neonatal origin. We established that this production is strictly
dependent on the “Thymic stromal lymphopoietin” (TSLP).
TLR4 gene expression during B cell ontogeny.
We showed that TLR4, a gene product involved in the innate response
to bacterial products such as LPS, is monoallelic expressed in B
cells from the stage of pre-B cells, and in bone marrow granulocytes.
The pattern of expression resembles the inactivation of the X chromosome.
We are presently studyng the role of TLR receptors on the surface
of B cells.