Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions

Stem cells and neuroblasts derived from mouse embryos undergo repeated asymmetric cell divisions, generating neural lineage trees similar to those of invertebrates. In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates. We investigated whether a mouse homologue m-numb had a similar role during mouse cortical development. Progenitor cells isolated from the embryonic mouse cortex were followed as they underwent their next cell division in vitro. Numb distribution was predominantly asymmetric during asymmetric cell divisions yielding a β-tubulin III− progenitor and a β-tubulin III+ neuronal cell (P/N divisions) and predominantly symmetric during divisions producing two neurons (N/N divisions). Cells from the numb knockout mouse underwent significantly fewer asymmetric P/N divisions compared to wild type, indicating a causal role for Numb. When progenitor cells derived from early (E10) cortex undergo P/N divisions, both daughters express the progenitor marker Nestin, indicating their immature state, and Numb segregates into the P or N daughter with similar frequency. In contrast, when progenitor cells derived from later E13 cortex (during active neurogenesis in vivo) undergo P/N divisions they produce a Nestin+ progenitor and a Nestin– neuronal daughter, and Numb segregates preferentially into the neuronal daughter. Thus during mouse cortical neurogenesis, as in Drosophila neurogenesis, asymmetric segregation of Numb could inhibit Notch activity in one daughter to induce neuronal differentiation. At terminal divisions generating two neurons, Numb was symmetrically distributed in approximately 80% of pairs and asymmetrically in 20%. We found a significant association between Numb distribution and morphology: most sisters of neuron pairs with symmetric Numb were similar and most with asymmetric Numb were different. Developing cortical neurons with Numb had longer processes than those without. Numb is expressed by neuroblasts and stem cells and can be asymmetrically segregated by both. These data indicate Numb has an important role in generating asymmetric cell divisions and diverse cell fates during mouse cortical development.

Download Full-text

Emerging mechanisms of asymmetric stem cell division

The Journal of Cell Biology ◽

10.1083/jcb.201807037 ◽

2018 ◽

Vol 217 (11) ◽

pp. 3785-3795 ◽

Cited By ~ 42

Author(s):

Zsolt G. Venkei ◽

Yukiko M. Yamashita

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Division ◽

Asymmetric Cell Division ◽

Binary Outcomes ◽

Cellular Mechanisms ◽

Asymmetric Cell Divisions ◽

Cell Divisions ◽

Dividing Cells ◽

Stem Cell Division

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.

Download Full-text

Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

The Journal of Cell Biology ◽

10.1083/jcb.201510104 ◽

2015 ◽

Vol 211 (4) ◽

pp. 737-739 ◽

Cited By ~ 5

Author(s):

Marisa M. Faraldo ◽

Marina A. Glukhova

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Cell Expansion ◽

Progenitor Cell ◽

Asymmetric Cell Divisions ◽

Stem Cell Expansion ◽

Cell Divisions ◽

Cell Fate Determinant ◽

Mammary Stem

In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny.

Download Full-text

C. elegansseam cells as stem cells: Wnt signaling and casein kinase Iα regulate asymmetric cell divisions in an epidermal progenitor cell type

Cell Cycle ◽

10.4161/cc.10.1.14329 ◽

2011 ◽

Vol 10 (1) ◽

pp. 23-22 ◽

Cited By ~ 2

Author(s):

David M. Eisenmann

Keyword(s):

Stem Cells ◽

Wnt Signaling ◽

Progenitor Cell ◽

Casein Kinase ◽

Cell Type ◽

Asymmetric Cell Divisions ◽

Cell Divisions

Download Full-text

Yukiko Yamashita: The centrosomes get there first

The Journal of Cell Biology ◽

10.1083/jcb.2016pi ◽

2013 ◽

Vol 201 (6) ◽

pp. 782-783

Author(s):

Caitlin Sedwick

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Asymmetric Cell Divisions ◽

Cell Divisions

Yamashita studies how germline stem cells orient their asymmetric cell divisions.

Download Full-text

Spindle orientation and epidermal morphogenesis

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0016 ◽

2013 ◽

Vol 368 (1629) ◽

pp. 20130016 ◽

Cited By ~ 43

Author(s):

Anita Kulukian ◽

Elaine Fuchs

Keyword(s):

Stem Cells ◽

Basement Membrane ◽

Cell Fate ◽

Mitotic Spindle ◽

Spindle Orientation ◽

Asymmetric Cell Divisions ◽

Daughter Cells ◽

Cell Divisions ◽

Molecular Machinery ◽

Asymmetric Partitioning

Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stem cells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.

Download Full-text