Publications by authors named "Qiutan Yang"

10 Publications

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Collective behaviours in organoids.

Curr Opin Cell Biol 2021 Jul 28;72:81-90. Epub 2021 Jul 28.

Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel. Petersplatz 1, 4001 Basel, Switzerland. Electronic address:

Collective behaviour emerges from interacting units within communities, such as migrating herds, swimming fish schools, and cells within tissues. At the microscopic level, collective behaviours include collective cell migration in development and cancer invasion, rhythmic gene expression in pattern formation, cell competition in homeostasis and cancer, force generation and mechano-sensing in morphogenesis. Studying the initiation and the maintenance of collective cell behaviours is key to understand the principles of development, regeneration and disease. However, the manifold influences of contributing factors in in vivo environments challenge the dissection of causalities in animal models. As an alternative model that has emerged to overcome this difficulty, in vitro three-dimensional organoid cultures provide a reductionist approach yet retain similarities with the in vivo tissue in cellular composition and tissue organisation. Here, we focus on recent progresses in studying collective behaviours in different organoid systems and discuss their advantages and the possibility of improvement for future applications.
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http://dx.doi.org/10.1016/j.ceb.2021.06.006DOI Listing
July 2021

Cell fate coordinates mechano-osmotic forces in intestinal crypt formation.

Nat Cell Biol 2021 07 21;23(7):733-744. Epub 2021 Jun 21.

Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.

Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.
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http://dx.doi.org/10.1038/s41556-021-00700-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611267PMC
July 2021

Engineering human knock-in organoids.

Nat Cell Biol 2020 03;22(3):261-263

Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.

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http://dx.doi.org/10.1038/s41556-020-0478-zDOI Listing
March 2020

The Invading Anchor Cell Induces Lateral Membrane Constriction during Vulval Lumen Morphogenesis in C. elegans.

Dev Cell 2017 08;42(3):271-285.e3

Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address:

During epithelial tube morphogenesis, linear arrays of cells are converted into tubular structures through actomyosin-generated intracellular forces that induce tissue invagination and lumen formation. We have investigated lumen morphogenesis in the C. elegans vulva. The first discernible event initiating lumen formation is the apical constriction of the two innermost primary cells (VulF). The VulF cells thereafter constrict their lateral membranes along the apicobasal axis to extend the lumen dorsally. Lateral, but not apical, VulF constriction requires the prior invasion of the anchor cell (AC). The invading AC extends actin-rich protrusions toward VulF, resulting in the formation of a direct AC-VulF interface. The recruitment of the F-BAR-domain protein TOCA-1 to the AC-VulF interface induces the accumulation of force-generating actomyosin, causing a switch from apical to lateral membrane constriction and the dorsal extension of the lumen. Invasive cells may induce shape changes in adjacent cells to penetrate their target tissues.
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http://dx.doi.org/10.1016/j.devcel.2017.07.008DOI Listing
August 2017

An in vivo EGF receptor localization screen in C. elegans Identifies the Ezrin homolog ERM-1 as a temporal regulator of signaling.

PLoS Genet 2014 May 1;10(5):e1004341. Epub 2014 May 1.

University of Zurich, Institute of Molecular Life Sciences, Zurich, Switzerland.

The subcellular localization of the epidermal growth factor receptor (EGFR) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding. Therefore, changes in EGFR localization and signaling are implicated in various human diseases, including different types of cancer. We have performed the first in vivo EGFR localization screen in an animal model by observing the expression of the EGFR ortholog LET-23 in the vulval epithelium of live C. elegans larvae. After systematically testing all genes known to produce an aberrant vulval phenotype, we have identified 81 genes regulating various aspects of EGFR localization and expression. In particular, we have found that ERM-1, the sole C. elegans Ezrin/Radixin/Moesin homolog, regulates EGFR localization and signaling in the vulval cells. ERM-1 interacts with the EGFR at the basolateral plasma membrane in a complex distinct from the previously identified LIN-2/LIN-7/LIN-10 receptor localization complex. We propose that ERM-1 binds to and sequesters basolateral LET-23 EGFR in an actin-rich inactive membrane compartment to restrict receptor mobility and signaling. In this manner, ERM-1 prevents the immediate activation of the entire pool of LET-23 EGFR and permits the generation of a long-lasting inductive signal. The regulation of receptor localization thus serves to fine-tune the temporal activation of intracellular signaling pathways.
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http://dx.doi.org/10.1371/journal.pgen.1004341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006739PMC
May 2014

Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis.

Sci China Life Sci 2011 Oct 29;54(10):897-903. Epub 2011 Oct 29.

Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development. The Xenopus LAP proteins show a conserved domain structure that is similar to their homologs in other vertebrates. In Xenopus embryos, these genes were detected in animal cap cells at the early gastrula stage. At later stages of development, they were widely expressed in epithelial tissues that are highly polar in nature, including the neural epithelia, optic and otic vesicles, and in the pronephros. These data suggest that the roles of the Xenopus LAP genes in the control of cell polarity and morphogenesis are conserved during early development. Erbin and lano show similar expression patterns in the developing head, suggesting potential functional interactions between the two molecules in vivo.
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http://dx.doi.org/10.1007/s11427-011-4224-4DOI Listing
October 2011

Xenopus Dbx2 is involved in primary neurogenesis and early neural plate patterning.

Biochem Biophys Res Commun 2011 Aug 23;412(1):170-4. Epub 2011 Jul 23.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.

The evolutionarily conserved Dbx homeodomain-containing proteins play important roles in the development of vertebrate central nervous system. In mouse, Dbx and Nkx6 have been suggested to be cross-repressive partners involved in the patterning of ventral neural tube. Here, we have isolated Xenopus Dbx2 and studied its developmental expression and function during neural development. Like XDbx1, from mid-neurula stage on, XDbx2 is expressed in stripes between the primary motoneurons and interneurons. At the tailbud stages, it is detected in the middle region of the neural tube. XDbx2 acts as a transcriptional repressor in vitro and over-expression of XDbx2 inhibits primary neurogenesis in Xenopus embryos. Over-expression of XDbx genes represses the expression of XNkx6.2 and vise versa. Knockdown of either XDbx1, XDbx2 or both by specific morpholinos induces lateral expansion of XNkx6.2 expression domains. These data reveal conserved roles for Dbx in primary neurogenesis and dorsoventral neural patterning in Xenopus.
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http://dx.doi.org/10.1016/j.bbrc.2011.07.068DOI Listing
August 2011

Overexpression of Trpp5 contributes to cell proliferation and apoptosis probably through involving calcium homeostasis.

Mol Cell Biochem 2010 Jun 31;339(1-2):155-61. Epub 2009 Dec 31.

Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 610041 Chengdu, People's Republic of China.

Trpp5 is one member of the polycystic kidney disease (PKD) family, which belongs to transient receptor potential (TRP) superfamily. Our previous study has shown that Trpp5 is developmentally expressed in mouse testis and overexpression of Trpp5 increases intracellular free calcium concentration in MDCK cells. However, the roles of this protein in cellular processes are largely unknown. Here, we demonstrated that Trpp5 resided in both cytoplasm and cell membrane of HEK293 cells. We found that overexpression of Trpp5 slightly increased the calcium current amplitude of HEK293 cells and shifted the reversal potential to a more negative value. Meanwhile, overexpression of Trpp5 suppressed proliferation of Hela cells via inhibiting DNA replication and induced apoptosis of Hela cells with morphological changes and accumulation of fragmented DNA. Collectively, these findings suggest that Trpp5 might involve calcium homeostasis contributing to cell proliferation and apoptosis.
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http://dx.doi.org/10.1007/s11010-009-0379-8DOI Listing
June 2010

Overexpression of FoxO1 causes proliferation of cultured pancreatic beta cells exposed to low nutrition.

Biochemistry 2010 Jan;49(1):218-25

Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.

Multiple lines of evidence have shown that the functional defect of pancreatic beta cells is the root cause of type 2 diabetes. FoxO1, a key transcription factor of fundamental cellular physiology and functions, has been implicated in this process. However, the underlying molecular mechanism is still largely unknown. Here, we show that the overexpression of FoxO1 promotes the proliferation of cultured pancreatic beta cells exposed to low nutrition, while no change in apoptosis was observed compared with the control group. Moreover, by using two specific inhibitors for PI3K and MAPK signaling, we found that FoxO1 might be the downstream transcription factor of these two pathways. Furthermore, a luciferase assay demonstrated that FoxO1 could regulate the expression of Ccnd1 at the transcription level. Collectively, our findings indicated that FoxO1 modulated by both MAPK and PI3K signaling pathways was prone to cause the proliferation, but not the apoptosis, of pancreatic beta cells exposed to low nutrition, at least partially, by regulating the expression of Ccnd1 at the transcription level.
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http://dx.doi.org/10.1021/bi901414gDOI Listing
January 2010

Success of murine embryo transfer increased by a modified transfer pipette.

J Reprod Dev 2009 Feb 20;55(1):94-7. Epub 2008 Nov 20.

Core Facility of Gene Engineered Mouse, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Embryos transfer is one of the most critical steps for generating genetically modified mice. Because of the limitations of the current transfer equipment and techniques, such as discharge of freshly transferred embryos and the necessity of sophisticated transfer skills, the success ratio of implantation may not well satisfy the requirements for mass production of high quality animals in the field of genetically modified mice. In this study, we describe a modified embryo transfer pipette with a syringe-like tip that can easily be applied to mouse embryo transfer. Using this improved method, we show that the procedures for mouse embryo implantation are simplified and easier to perform; moreover, the viability rate of mouse embryos is 20% higher than that achieved with conventional methods. Our modified tool and improved transfer technique are effective, time-saving and less invasive, resulting in increased success of embryo transfer.
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http://dx.doi.org/10.1262/jrd.20090DOI Listing
February 2009
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