Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division

Abstract

It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive whether primitive hematopoietic cells in mammals actually can divide asymmetrically. In our experiments we have challenged this question and analyzed the developmental capacity of separated offspring of primitive human hematopoietic cells at a single-cell level. We show for the first time that the vast majority of the most primitive, in vitro-detectable human hematopoietic cells give rise to daughter cells adopting different cell fates; 1 inheriting the developmental capacity of the mother cell, and 1 becoming more specified. In contrast, approximately half of the committed progenitor cells studied gave rise to daughter cells, both of which adopted the cell fate of their mother. Although our data are compatible with the model of asymmetric cell division, other mechanisms of cell fate specification are discussed. In addition, we describe a novel human hematopoietic progenitor cell that has the capacity to form natural killer (

Role of symmetric and asymmetric division of stem cells in developing drug resistance

“…This result is not surprising for the probability of a symmetric differentiation, b, which is typically estimated to be very small. However, the estimated value of the asymmetric division probability a is interesting, because it has been observed that for healthy hematopoietic stem cells, a should be close to 1, and generally above 0.9 (18,19).…”

“…By Eqs. 18, 13, and 17, we have that the probability of having resistant cancer stem cells at the time of detection is 1 − C 1 − Cðx∕MÞ ; [19] where C ¼ DþLb Lð1−a−bÞ . By replacing the summation with an integral, and with a change of variable, we get P R ≈ 1 − exp − uMð1 − a 2 − bÞ ð1 − a − bÞ…”

New relationships of human hematopoietic lineages facilitate detection of multipotent hematopoietic stem and progenitor cells

“…1 According to this model, HSCs give rise to MPPs, which, in turn, create LMPPs and EMPs, maybe by means of asymmetric cell division. 19,20 EMPs harbor the potential to form megakaryocytic and erythroid progenitors (MEP) as well as eosinophil/ basophil progenitors (EoBPs), which very probably also contain mast cell potentials. In contrast, LMPPs comprise the capability to form GMPs being restricted to form neutrophils and monocytes/macrophages and lymphocyte potentials that might be realized via multilymphoid progenitors (MLPs) that have recently been described by John Dick's group.…”

“…1 It will be interesting to note whether any of the published conditions, e.g., those which have been found to expand serially transplantable SRCs, [29][30][31] allow expansion of CD133 + CD34 + cells containing erythroid potentials. The finding that MPP potentials are lost in the presence of early acting cytokines with the first cell division, which occurs after 2-3 d in vitro, 19,20 brings up another aspect for HSC transplantation. It has been discussed whether cytokine stimulation of HSC-containing grafts increase their homing and engraftment rates.…”

Concise Review: Asymmetric Cell Divisions in Stem Cell Biology

“…This assumption was initially based on the outcome of so-called paired daughter cell experiments. Different groups separated daughter cells of single human hematopoietic stem and progenitor cells (HSPCs), and consistently reported that in 20%-40% of the cases both daughter cells showed different proliferation rates and differentiation capacities [54][55][56][57]. Even though this functional asymmetry of arising daughter cells was explained by ACD, theoretically it could have been established by post-mitotic communication processes between identical daughter cells [1].…”