Project Details
Projekt
Functions of laminin isoforms during hematopoietic stem cell development
Applicant
Professor Dr. Gerd Klein
Subject Area
Dermatology
Term
from 2002 to 2005
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5394022
Hematopoietic stem cells are characterized by their potency for self-renewal as well as by their potential to differentiate into various cell lineages. How these developmental decisions are regulated is largely unknown but influences of the hematopoietic microenvironment, including the extracellular matrix, are suspected to be involved in these regulatory processes. Laminins are heterotrimeric molecules of the extracellular matrix occuring in several isoforms. The most prominent members of the laminin gene family in the human bone marrow are the isoforms LN-8/9 and LN-10/11. Previous work has shown that LN-10/11 is both an adhesive and a mitogenic substrate for human hematopoietic progenitor cells. In addition, LN-10/11 can also be involved in stem cell mobilization and differentiation. The aim of the current project is to characterize cellular receptors on hematopoietic stem cells responsible for the induction of proliferation and differentiation by LN-10/11. Mass spectrometry will be used to identify the fragments generated by enzymatic digestion of LN-10/11 which are responsible for an increased cell migration of hematopoietic progenitor cells. The functional analysis of LN-8/9 with hematopoietic stem and progenitor cells as well as the characterization of a newly identified laminin isoform present in the human bone marrow is another focus of this research project. These studies are aimed to provide insight into the molecular interactions of bone marrow stem cells with specific components of the hematopoietic microenvironment.
DFG Programme
Priority Programmes
