Good news!
"... Recently, ... found that CXCL12, a signaling protein, may solve this problem.1 When the researchers exposed mice erythroblasts, or immature red blood cells, to CXCL12, they triggered enucleation. Their findings, reported in Science Signaling, may help advance efforts in making blood in the lab. ..."
"... deciphered a further intermediate step towards a complete understanding of the cellular processes: the molecular signal, chemokine CXCL12, triggers the expulsion of the nucleus by the red blood cell precursors, a key step in the development of red blood cells. ..."
From the editor's summary and abstract:
"Editor’s summary
Signaling by the chemokine CXCL12 through its receptor CXCR4 promotes cell migration during embryonic development and immune surveillance and to sites of infection and inflammation. Gutjahr et al. found that bone marrow–derived CXCL12 activated CXCR4 on mouse bone marrow erythroblasts, the precursors of red blood cells (erythrocytes), to promote erythroblast differentiation, rather than their migration, through pathways involving intracellular and nuclear CXCR4 signaling.
Knockout of CXCR4 selectively in erythroblasts inhibited erythrocyte generation in mice. These findings indicate that CXCL12-CXCR4 signaling promotes erythropoiesis, suggesting that it should be investigated for the treatment of erythrocyte pathologies. ...
Abstract
The chemokine CXCL12 signals through its receptor CXCR4 to induce the migration of all leukocyte types and multiple other cell types. Here, we report that CXCR4 is expressed in mouse erythroblasts, the bone marrow erythroid precursors, in which it stimulates erythrocyte generation instead of chemotaxis.
CXCR4 signaling promoted homeostatic erythroblast maturation and increased the expression of genes mainly involved in metabolism and chromatin organization. Consequently, genetic depletion of CXCR4 in erythroblasts inhibited late erythropoiesis and diminished bone marrow erythroid outputs.
Binding of CXCL12 to CXCR4 stimulated its rapid endocytosis and translocation together with Gαi or phosphorylated β-arrestin1 into distinct intracellular compartments, including the nuclear envelope and nucleus.
CXCL12 signaling promoted erythroblast elongation and the condensation and excentric positioning of nuclei and stimulated rapid perinuclear Ca2+ transients that immediately preceded erythroblast enucleation.
These findings highlight previously uncharacterized physiological roles for CXCR4 and bone marrow–derived CXCL12 in erythropoiesis."
Breakthrough in Artificial Blood Production (original news release) "Scientists have been working on the artificial production of blood for several decades. Making a new discovery, researchers from the Institute for Cellular Biology and Immunology Thurgau at the University of Konstanz, in collaboration with Queen Mary University of London, have come an important step closer to this goal."
Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation (open access)
Fig. 5. CXCL12-stimulated erythroblast elongation, nuclear polarization, chromatin condensation, and enucleation.
Julia Christine Gutjahr (her last name means good year, source)
No comments:
Post a Comment