Article,

Multipotent Hematopoietic Progenitors Divide Asymmetrically to Create Progenitors of the Lymphomyeloid and Erythromyeloid Lineages

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Stem Cell Reports, 3 (6): 1058 - 1072 (2014)
DOI: http://dx.doi.org/10.1016/j.stemcr.2014.09.016

Abstract

Summary Hematopoietic stem and progenitor cells (HSPCs) can self-renew and create committed progenitors, a process supposed to involve asymmetric cell divisions (ACDs). Previously, we had linked the kinetics of \CD133\ expression with \ACDs\ but failed to detect asymmetric segregation of classical \CD133\ epitopes on fixed, mitotic HSPCs. Now, by using a novel anti-CD133 antibody (HC7), we confirmed the occurrence of asymmetric \CD133\ segregation on paraformaldehyde-fixed and living HSPCs. After showing that \HC7\ binding does not recognizably affect biological features of human HSPCs, we studied \ACDs\ in different \HSPC\ subtypes and determined the developmental potential of arising daughter cells at the single-cell level. Approximately 70% of the \HSPCs\ of the multipotent progenitor (MPP) fraction studied performed ACDs, and about 25% generated lymphoid-primed multipotent progenitor (LMPP) as wells as erythromyeloid progenitor (EMP) daughter cells. Since \MPPs\ hardly created daughter cells maintaining \MPP\ characteristics, our data suggest that under conventional culture conditions, \ACDs\ are lineage instructive rather than self-renewing.

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