Ana CUMANO
Lymphopoiesis
Lymphopoiesis
KEYWORDS: Lymphopoiesis, hematopoiesis
Innate lymphoid cells, cytokines
Thymus
Mice
Innate lymphoid cells, cytokines
Thymus
Mice
We have been interested in understanding the mechanisms that control the establishment of the immune system.
We concentrate on two main lines of research.
1. Understanding the molecular mechanisms underlying lymphoid lineage commitment.
Manipulating the adult immune system, with a view to treat for example immunodeficiencies or lymphoproliferative diseases, requires a deep understanding of how the system is established and develops during embryonic and neonatal life. The interest devoted to deciphering the molecular basis for lymphoid lineage commitment derives from that conviction. As a general strategy we use our competence in mammalian embryology and flow cytometry to study lymphoid organs, defining and isolating discrete progenitor subsets at different stages of embryonic development, that are then characterized at the molecular and functional levels.
2. Dissecting the environmental signals that sustain self-renewal and differentiation of hematopoietic progenitors.
Hematopoietic stem cells (HSC) expand under physiologic conditions in two different anatomical sites and developmental scenarios. One is the fetal liver (FL), which is colonized by a limited number of (between 500 and 1,000) HSCs in the mouse, generated only during embryonic development in the dorsal aorta. The other is the developing and growing bone marrow (BM) that is colonized by FL-derived, blood borne HSCs that expand during pre- and postnatal growth. After the 4th week of age, HSCs become mostly quiescent dividing only once every 2-3 months. Asymmetric cell division maintains the pool of HSCs while differentiation ensures constant blood cell production.
The aim of our project is to single out regulators of HSC expansion that can be directly translated into therapies and products. To that end, we developed assays that directly model these two distinct physiologic scenarios.
We concentrate on two main lines of research.
1. Understanding the molecular mechanisms underlying lymphoid lineage commitment.
Manipulating the adult immune system, with a view to treat for example immunodeficiencies or lymphoproliferative diseases, requires a deep understanding of how the system is established and develops during embryonic and neonatal life. The interest devoted to deciphering the molecular basis for lymphoid lineage commitment derives from that conviction. As a general strategy we use our competence in mammalian embryology and flow cytometry to study lymphoid organs, defining and isolating discrete progenitor subsets at different stages of embryonic development, that are then characterized at the molecular and functional levels.
2. Dissecting the environmental signals that sustain self-renewal and differentiation of hematopoietic progenitors.
Hematopoietic stem cells (HSC) expand under physiologic conditions in two different anatomical sites and developmental scenarios. One is the fetal liver (FL), which is colonized by a limited number of (between 500 and 1,000) HSCs in the mouse, generated only during embryonic development in the dorsal aorta. The other is the developing and growing bone marrow (BM) that is colonized by FL-derived, blood borne HSCs that expand during pre- and postnatal growth. After the 4th week of age, HSCs become mostly quiescent dividing only once every 2-3 months. Asymmetric cell division maintains the pool of HSCs while differentiation ensures constant blood cell production.
The aim of our project is to single out regulators of HSC expansion that can be directly translated into therapies and products. To that end, we developed assays that directly model these two distinct physiologic scenarios.
