Article (Scientific journals)
Genesis of clone size heterogeneity in megakaryocytic and other hemopoietic colonies: the stochastic model revisited
Paulus, Jean-Michel; Levin, Jack; Debili, Najet et al.
2001In Experimental Hematology, 29 (nd), p. 1256-69
Peer reviewed
 

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Keywords :
Hemopoiesis; Megakaryocytes; Clonal heterogeneity
Abstract :
[en] OBJECTIVE: We previously showed that the distributions of the numbers of doublings (NbD) undergone by individual megakaryocyte progenitors before commitment to polyploidization are markedly skewed and can consistently be fitted to straight lines when plotted on semilogarithmic coordinates. The slope of such lines, which yields the probability of polyploidization per doubling, is made less steep by stimulators of megakaryocyte colony formation and is less steep in mixed erythroid-megakaryocyte than in pure megakaryocyte colonies. Therefore, megakaryocytopoiesis provides a unique model for the study of clonal heterogeneity in a hemopoietic lineage, which is the subject of this review. DATA SOURCES: Articles relevant to the interpretation of these data were selected from the authors' and public databases. DATA SYNTHESIS: Exponential NbD distributions were first explained by postulating that following the assembly of thrombopoiesis-specific regulators, megakaryocyte progenitors require only a single random event to arrest proliferation and commit to polyploidization. However, this stochastic model was refuted by data indicating that intrinsic properties of individual progenitors affect the NbD they achieve. We suggest that the unequal repartition of critical compounds (including receptors, signaling molecules, and gene regulators) inherent in the stem cell-progenitor transition causes a heritable heterogeneity in megakaryocyte progenitor responsiveness to polyploidization inducers. This model would be compatible with 1) the evidence for intraclonal synchronization in megakaryocyte and other hemopoietic clones generated by committed progenitors; 2) the low probability of polyploidization of the relatively insensitive bipotent megakaryocyte progenitors; and 3) the thesis that stimulators act in part by recruiting megakaryocyte progenitor cells endowed with lesser responsiveness to polyploidization inducers and higher proliferative potential. CONCLUSION: The responsiveness of individual megakaryocyte progenitors to polyploidization inducers may be a major determinant of the exponential shape of NbD distributions.
Disciplines :
General & internal medicine
Author, co-author :
Paulus, Jean-Michel ;  Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Levin, Jack
Debili, Najet
Albert, Adelin  ;  Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Vainchenker, William
Language :
English
Title :
Genesis of clone size heterogeneity in megakaryocytic and other hemopoietic colonies: the stochastic model revisited
Publication date :
2001
Journal title :
Experimental Hematology
ISSN :
0301-472X
eISSN :
1873-2399
Publisher :
Elsevier
Volume :
29
Issue :
nd
Pages :
1256-69
Peer reviewed :
Peer reviewed
Name of the research project :
Hemopoiesis, megakaryopoiesis
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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since 10 January 2013

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