Stem cell niche exit in C. elegans via orientation and segregation of daughter cells by a cryptic cell outside the niche.

Kacy L Gordon,David R Sherwood,Jay W Zussman,Xin Li,Camille Miller

doi:10.7554/elife.56383

Kacy L Gordon, David R Sherwood + Show 3 more

Open Access

https://doi.org/10.7554/elife.56383

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Abstract

Stem cells reside in and rely upon their niche to maintain stemness but must balance self-renewal with the production of daughters that leave the niche to differentiate. We discovered a mechanism of stem cell niche exit in the canonical C. elegans distal tip cell (DTC) germ stem cell niche mediated by previously unobserved, thin, membranous protrusions of the adjacent somatic gonad cell pair (Sh1). A disproportionate number of germ cell divisions were observed at the DTC-Sh1 interface. Stem-like and differentiating cell fates segregated across this boundary. Spindles polarized, pairs of daughter cells oriented between the DTC and Sh1, and Sh1 grew over the Sh1-facing daughter. Impeding Sh1 growth by RNAi to cofilin and Arp2/3 perturbed the DTC-Sh1 interface, reduced germ cell proliferation, and shifted a differentiation marker. Because Sh1 membrane protrusions eluded detection for decades, it is possible that similar structures actively regulate niche exit in other systems.

Highlights

To investigate how the elaborate distal tip cell (DTC) germ line stem cell niche interacts with other cells in the gonad we used CRISPR/Cas9-mediated genome editing (Dickinson et al, 2015; Dickinson et al, 2013) to endogenously tag cell membrane-localized gap junction proteins (INX-8 and INX-9) that were previously found to be expressed in the DTC and the gonadal sheath cells (Starich et al, 2014)
Given that our results suggested that the DTC-Sheath cell pair 1 (Sh1) interface promoted proliferation, we assessed the effect of Sh1 and the underlying germ cells by perturbing its position with unc-60 RNAi
Challenges of in vivo imaging have recently been overcome in the zebrafish larval hematopoietic niche, mammalian epidermal stem cell niche, and mouse intestinal crypt, revealing important behaviors such as ‘endothelial cuddling’ of stem cells (Tamplin et al, 2015), different rates of division across stem cells and their daughters, (Rompolas et al, 2012), and different trajectories for stem cells depending on their position within the niche (Ritsma et al, 2014)

Summary

Introduction

Stem cells and their associated supportive niche cells are centrally important to development (Murry and Keller, 2008; Zhu and Huangfu, 2013), homeostatic tissue maintenance (Biteau et al, 2011; Blanpain and Fuchs, 2009; Snippert et al, 2010; Wilson et al, 2008), aging (Rao and Mattson, 2001), regeneration (Sanchez Alvarado and Yamanaka, 2014), cancer (Reya et al, 2001), and tissue engineering (Ruder et al, 2011). Examples include stochastic displacement in the mammalian intestine (van der Flier and Clevers, 2009), migration in the larval tracheal system of Drosophila (Chen and Krasnow, 2014), oriented division to a basal lamina in the mammalian epidermis (Poulson and Lechler, 2010), and oriented division to the niche cells in the Drosophila ovary (Casanueva and Ferguson, 2004)

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