Control of Intestinal Cell Fate by Dynamic Mitotic Spindle Repositioning Influences Epithelial Homeostasis and Longevity

Hu, Daniel Jun-Kit; Jasper, Heinrich

doi:10.1016/j.celrep.2019.08.014

Cited by 44 publications

(74 citation statements)

References 89 publications

(130 reference statements)

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“…Consistent with earlier reports (Hu and Jasper, 2019;Jin et al, 2017;O'Brien et al, 2011), approximately 23% of all clones were products of symmetric divisions in CR flies (Fig. 7J).…”

Section: Brevis Alters Progenitor Cell Identity and Promotes Symmesupporting

confidence: 93%

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Ferguson

Petkau

Shin

et al. 2019

Preprint

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Commensal bacteria regulate the growth and differentiation of intestinal epithelial cells.Deregulated growth compromises the efficacy of critical repair pathways, and promotes tissue dysplasia and tumorigenesis. Despite the importance of bacteria-derived cues for tissue homeostasis, we know little about how intestinal commensals directly influence stem cell division programs. In this study, we examined the effects of common fly symbionts on tissue growth and tumorigenesis in the Drosophila intestine. We identified the cell wall of Lactobacillus brevis as a potent stimulator of Notch-deficient tumor growth. Our work uncovered a complex feed-forward loop between tumor growth and intestinal colonization by L. brevis. Mechanistically, we showed that L. brevis disrupts the expression and apicobasal distribution of integrins in intestinal progenitors, and supports an increase in stem cell numbers characterized by elevated numbers of symmetric stem cell divisions. Collectively, this work highlights host-commensal interactions that influence intestinal growth and stem cell division.

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“…Consistent with earlier reports (Hu and Jasper, 2019;Jin et al, 2017;O'Brien et al, 2011), approximately 23% of all clones were products of symmetric divisions in CR flies (Fig. 7J).…”

Section: Brevis Alters Progenitor Cell Identity and Promotes Symmesupporting

confidence: 93%

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Ferguson

Petkau

Shin

et al. 2019

Preprint

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“…Furthermore, differential Notch activities due to the Par complex activity induce distinct cellular differentiation pathways (Guo and Ohlstein, 2015). Recent work has also shown that the spindle orientation in ISCs is tightly linked with cell fate, where planar orientation gives rise to two ISCs and angular orientation generates a ISC-EB pair (Hu and Jasper, 2019). Here, through analyzing different mitotic phases of ISCs, separable old versus new H3 distribution are detectable in prophase and prometaphase ISCs, indicating that this asymmetry is intrinsically established prior to mitosis (Figure 6A).…”

Section: Discussionmentioning

confidence: 99%

Asymmetric histone inheritance regulates stem cell fate inDrosophilamidgut

Zion

Chen

2020

Preprint

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A fundamental question in developmental biology is how distinct cell fates are established and maintained through epigenetic mechanisms in multicellular organisms. Here, we report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically inherited by the distinct daughter cells during asymmetric division of Drosophila intestinal stem cells (ISCs). By contrast, in symmetrically dividing ISCs that produce two self-renewed stem cells, old and new H3 and H4 show symmetric inheritance patterns. These results indicate that asymmetric histone inheritance is tightly associated with the distinct daughter cell fates. To further understand the biological significance of this asymmetry, we express a mutant histone that compromises asymmetric histone inheritance pattern. We find increased symmetric ISC division and ISC tumors during aging under this condition. Together, our results demonstrate that asymmetric histone inheritance is important for establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in asymmetrically dividing male germline stem cells in Drosophila. Therefore, this work sheds light on the principles of histone inheritance in regulating stem cell fate in vivo.

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“…Injury stimulus may impact the mode of regeneration, as symmetric ISC divisions are not reported to increase following P. entomophila infection (Jin et al, 2017). Related to this idea, ISC spindle orientation was recently tied to division outcome (symmetric versus asymmetric), and was shown to be differentially regulated by varying stress stimuli (Hu and Jasper, 2019). Importantly, the injured mouse gut is also capable of ISC-mediated regeneration (Barriga et al, 2017;Metcalfe et al, 2014;Yan et al, 2012).…”

Section: The Midgutmentioning

confidence: 99%

Model systems for regeneration: Drosophila

2020

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Drosophila melanogaster has historically been a workhorse model organism for studying developmental biology. In addition, Drosophila is an excellent model for studying how damaged tissues and organs can regenerate. Recently, new precision approaches that enable both highly targeted injury and genetic manipulation have accelerated progress in this field. Here, we highlight these techniques and review examples of recently discovered mechanisms that regulate regeneration in Drosophila larval and adult tissues. We also discuss how, by applying these powerful approaches, studies of Drosophila can continue to guide the future of regeneration research.

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Control of Intestinal Cell Fate by Dynamic Mitotic Spindle Repositioning Influences Epithelial Homeostasis and Longevity

Cited by 44 publications

References 89 publications

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Asymmetric histone inheritance regulates stem cell fate inDrosophilamidgut

Model systems for regeneration: Drosophila

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