High proliferative potential-quiescent cells: a working model to study primitive quiescent hematopoietic cells.
Human adult hematopoietic stem cells are mostly quiescent or slow cycling. We have previously demonstrated that blocking of transforming growth factor-beta1 (TGF-beta1) is able to activate, in the presence of cytokines, primitive quiescent hematopoietic multipotent progenitors which could not grow in a two week semi-solid culture assay (short term culture). We have also shown that anti-TGF-beta1 can up-modulate c-KIT, the receptor of the stem cell factor (steel factor). To elucidate whether TGF-beta1 plays a central role in controlling the quiescence of hematopoietic primitive cells, it was necessary to demonstrate, as detailed in this study, that: (1) whatever the cytokine combination tested, addition of anti-TGF-beta1 releases from quiescence multipotent progenitors with a significantly higher hematopoietic potential than those activated by cytokines alone. (2) Other important cytokine receptors controlling the most primitive hematopoietic cells such as FLT3 and the IL6 receptor (IL6-R) are down-modulated by TGF-beta1 but rapidly up-modulated by anti-TGF-beta1. (3) Anti-TGF-beta1-sensitive multipotent and high proliferative potential progenitors express these cytokine receptors at a low level (FLT3(low) and IL6-Rlow). According to these results, we propose the working model of 'High Proliferative Potential-Quiescent cells' to refer to these primitive hematopoietic multipotent progenitors that are highly sensitive to the growth inhibitory effect of TGF-beta1. This model could be valid not only to study the human hematopoietic quiescent progenitors but also for other somatic stem cell systems.
Fortunel
N
N
Centre National de la Recherche Scientifique, UPR 9044, 94800 Villejuif, France.
Batard
P
P
Hatzfeld
A
A
Monier
M N
MN
Panterne
B
B
Lebkowski
J
J
Hatzfeld
J
J
D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005312:Fetal Blood; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007399:Interphase / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000494:pharmacology; D008954:Models, Biological; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D018952:Antigens, CD34; D008565:Membrane Proteins; D019947:Receptors, Interleukin-6; D016212:Transforming Growth Factor beta; C084881:flt3 ligand protein; D016222:Fibroblast Growth Factor 2