Emerging mechanisms of asymmetric stem cell division

Abstract

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

A new role for Notch in the control of polarity and asymmetric cell division of developing T cells

“…It is well established that Notch controls diversification in cell fate in a number of developmental systems. However, most of the proposed mechanisms assume that Notch executes decisions that have been made stochastically or are imposed by unequal expression of regulators of Notch (Dewey et al, 2015;Schweisguth, 2015;Venkei et al, 2018). Here, we demonstrate that Notch1 can directly trigger asymmetry in daughter cells, by steering ACD and by partitioning itself asymmetrically in the two daughter cells (Fig.…”

“…ACD requires that polarity is coupled with orientation of the mitotic spindle (Venkei et al, 2018). We next asked whether the protein asymmetry triggered by Notch ligation was coordinated with the mitotic spindle.…”

“…This is achieved by sequential bifurcations in the fate of daughter cells following cell division. Fate bifurcation is driven by various means, including random differences in the daughters, different positional cues, or controlled segregation of fate determinants differentially into the two daughter cells, a process termed Asymmetric Cell Division (ACD) (Dewey et al, 2015;Schweisguth, 2015;Venkei et al, 2018). A common mediator of fate bifurcation, which uses all of these processes, is the Notch signalling pathway (Artavanis-Tsakonas et al, 1999;Fortini, 2009;Liu et al, 2017;Sjoqvist et al, 2017).…”

“…Indeed, some of the most frequently observed fate determinants controlled by ACD are the Notch regulators, Numb and α-Adaptin (Daeden et al, 2018;Dewey et al, 2015;Rhyu et al, 1994;Schweisguth, 2015). Consequently, the prevailing view is that, although an important executor of cell fate, Notch does not directly determine the direction of bifurcation in fate (Schweisguth, 2015;Venkei et al, 2018).…”

Asymmetric Division Promotes Therapeutic Resistance in Glioblastoma Stem Cells

“…Central to the identity of CSCs is the ability to execute multiple modes of cell division. Asymmetric cell division (ACD) is a cellular mechanism to generate heterogeneity while simultaneously maintaining a stem cell population (Venkei and Yamashita, 2018). ACD has been observed in multiple advanced cancers Lathia et al, 2011;Srinivasan et al, 2016;Wang et al, 2016), yet its functional contribution to tumorigenesis is not well understood.…”