MPI-CBG Publications

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Seungmin Han, Juergen Fink, David J. Jörg, Eunmin Lee, Min Kyu Yum, Lemonia Chatzeli, Sebastian R Merker, Manon Josserand, Teodora Trendafilova, Amanda Andersson-Rolf, Catherine Dabrowska, Hyunki Kim, Ronald Naumann, Ji-Hyun Lee, Nobuo Sasaki, Richard Lester Mort, Onur Basak, Hans Clevers, Daniel E Stange, Anna Philpott, Jong Kyoung Kim, Benjamin D Simons, Bon-Kyoung Koo
Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells.
Cell Stem Cell, 25(3) 342-356 (2019)
PubMed Source

The gastric corpus epithelium is the thickest part of the gastrointestinal tract and is rapidly turned over. Several markers have been proposed for gastric corpus stem cells in both isthmus and base regions. However, the identity of isthmus stem cells (IsthSCs) and the interaction between distinct stem cell populations is still under debate. Here, based on unbiased genetic labeling and biophysical modeling, we show that corpus glands are compartmentalized into two independent zones, with slow-cycling stem cells maintaining the base and actively cycling stem cells maintaining the pit-isthmus-neck region through a process of "punctuated" neutral drift dynamics. Independent lineage tracing based on Stmn1 and Ki67 expression confirmed that rapidly cycling IsthSCs maintain the pit-isthmus-neck region. Finally, single-cell RNA sequencing (RNA-seq) analysis is used to define the molecular identity and lineage relationship of a single, cycling, IsthSC population. These observations define the identity and functional behavior of IsthSCs.

@article{Han7480,
author={Seungmin Han, Juergen Fink, David J. Jörg, Eunmin Lee, Min Kyu Yum, Lemonia Chatzeli, Sebastian R Merker, Manon Josserand, Teodora Trendafilova, Amanda Andersson-Rolf, Catherine Dabrowska, Hyunki Kim, Ronald Naumann, Ji-Hyun Lee, Nobuo Sasaki, Richard Lester Mort, Onur Basak, Hans Clevers, Daniel E Stange, Anna Philpott, Jong Kyoung Kim, Benjamin D Simons, Bon-Kyoung Koo},
title={Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells.},
journal ={Cell stem cell},
volume={25},
issue ={3},
pages={342--356},
year=2019
}

Kai Schuhmann, HongKee Moon, Henrik Thomas, Jacobo Miranda Ackerman, Michael Groessl, Nicolai Wagner, Markus Kellmann, Ian Henry, André Nadler, Andrej Shevchenko
Quantitative Fragmentation Model for Bottom-up Shotgun Lipidomics.
Anal Chem, Art. No. doi: 10.1021/acs.analchem.9b03270 (2019)
PubMed Source

Quantitative bottom-up shotgun lipidomics relies on molecular species-specific "signature" fragments consistently detectable in MS/MS spectra of analytes and standards. Molecular species of glycerophospholipids are typically quantified using carboxylate fragments of their fatty acid moieties produced by higher-energy collisional dissociation of their molecular anions. However, employing standards whose fatty acids moieties are similar, yet not identical to the target lipids could severely compromise their quantification. We developed a generic and portable fragmentation model implemented in the open-source LipidXte software that harmonizes the abundances of carboxylate anion fragments originating from fatty acid moieties having different sn-1/2 position at the glycerol backbone, length of the hydrocarbon chain, number and location of double bonds. The post-acquisition adjustment enables unbiased absolute (molar) quantification of glycerophospholipid species independent of instrument settings, collision energy, and employed internal standards.

@article{Schuhmann7481,
author={Kai Schuhmann, HongKee Moon, Henrik Thomas, Jacobo Miranda Ackerman, Michael Groessl, Nicolai Wagner, Markus Kellmann, Ian Henry, André Nadler, Andrej Shevchenko},
title={Quantitative Fragmentation Model for Bottom-up Shotgun Lipidomics.},
journal ={Analytical chemistry},
volume={},
pages={1--1},
year=2019
}

Elisabeth Knust, Kai Simons
Suzanne Eaton (1959-2019): A pioneer in quantitative tissue morphogenesis.
J Cell Biol, 218(9) 2819-2821 (2019)
PubMed Source

@article{Knust7506,
author={Elisabeth Knust, Kai Simons},
title={Suzanne Eaton (1959-2019): A pioneer in quantitative tissue morphogenesis.},
journal ={The Journal of cell biology},
volume={218},
issue ={9},
pages={2819--2821},
year=2019
}

Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust
Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.
Dev Biol, 453(1) 56-67 (2019)
PubMed Source

Photoreceptor cells (PRCs) across the animal kingdom are characterized by a stacking of apical membranes to accommodate the high abundance of photopigment. In arthropods and many other invertebrate phyla PRC membrane stacks adopt the shape of densely packed microvilli that form a structure called rhabdomere. PRCs and surrounding accessory cells, including pigment cells and lens-forming cells, are grouped in stereotyped units, the ommatidia. In larvae of holometabolan insects, eyes (called stemmata) are reduced in terms of number and composition of ommatidia. The stemma of Drosophila (Bolwig organ) is reduced to a bilateral cluster of subepidermal PRCs, lacking all other cell types. In the present paper we have analyzed the development and fine structure of the Drosophila larval PRCs. Shortly after their appearance in the embryonic head ectoderm, PRC precursors delaminate and lose expression of apical markers of epithelial cells, including Crumbs and several centrosome-associated proteins. In the early first instar larva, PRCs show an expanded, irregularly shaped apical surface that is folded into multiple horizontal microvillar-like processes (MLPs). Apical PRC membranes and MLPs are covered with a layer of extracellular matrix. MLPs are predominantly aligned along an axis that extends ventro-anteriorly to dorso-posteriorly, but vary in length, diameter, and spacing. Individual MLPs present a "beaded" shape, with thick segments (0.2-0.3 μm diameter) alternating with thin segments (>0.1 μm). We show that loss of the glycoprotein Chaoptin, which is absolutely essential for rhabdomere formation in the adult PRCs, does not lead to severe abnormalities in larval PRCs.

@article{Hartenstein7405,
author={Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust},
title={Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.},
journal ={Developmental biology},
volume={453},
issue ={1},
pages={56--67},
year=2019
}

Valerie Siahaan, Jochen Krattenmacher, Anthony Hyman, Stefan Diez, Amayra Hernández-Vega, Zdenek Lansky, Marcus Braun
Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes.
Nat Cell Biol, 21(9) 1086-1092 (2019)
PubMed Source

Tau is an intrinsically disordered protein, which diffuses on microtubules1. In neurodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules are correlated with axonal degeneration2. Tau can protect microtubules from microtubule-degrading enzymes such as katanin3. However, how tau carries out this regulatory function is still unclear. Here, using in vitro reconstitution, we show that tau molecules on microtubules cooperatively form cohesive islands that are kinetically distinct from tau molecules that individually diffuse on microtubules. Dependent on the tau concentration in solution, the islands reversibly grow or shrink by addition or release of tau molecules at their boundaries. Shielding microtubules from kinesin-1 motors and katanin, the islands exhibit regulatory qualities distinct from a comparably dense layer of diffusible tau. Superprocessive kinesin-8 motors penetrate the islands and cause their disassembly. Our results reveal a microtubule-dependent phase of tau that constitutes an adaptable protective layer on the microtubule surface. We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behaviour and potentially compete with tau in regulating access to the microtubule surface.

@article{Siahaan7510,
author={Valerie Siahaan, Jochen Krattenmacher, Anthony Hyman, Stefan Diez, Amayra Hernández-Vega, Zdenek Lansky, Marcus Braun},
title={Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes.},
journal ={Nature cell biology},
volume={21},
issue ={9},
pages={1086--1092},
year=2019
}

Gabriella Shull, Christiane Haffner, Wieland Huttner, Suhasa B Kodandaramaiah, Elena Taverna
Robotic platform for microinjection into single cells in brain tissue.
EMBO Rep, Art. No. e47880 (2019)
PubMed Source

Microinjection into single cells in brain tissue is a powerful technique to study and manipulate neural stem cells. However, such microinjection requires expertise and is a low-throughput process. We developed the "Autoinjector", a robot that utilizes images from a microscope to guide a microinjection needle into tissue to deliver femtoliter volumes of liquids into single cells. The Autoinjector enables microinjection of hundreds of cells within a single organotypic slice, resulting in an overall yield that is an order of magnitude greater than manual microinjection. The Autoinjector successfully targets both apical progenitors (APs) and newborn neurons in the embryonic mouse and human fetal telencephalon. We used the Autoinjector to systematically study gap-junctional communication between neural progenitors in the embryonic mouse telencephalon and found that apical contact is a characteristic feature of the cells that are part of a gap junction-coupled cluster. The throughput and versatility of the Autoinjector will render microinjection an accessible high-performance single-cell manipulation technique and will provide a powerful new platform for performing single-cell analyses in tissue for bioengineering and biophysics applications.

@article{Shull7503,
author={Gabriella Shull, Christiane Haffner, Wieland Huttner, Suhasa B Kodandaramaiah, Elena Taverna},
title={Robotic platform for microinjection into single cells in brain tissue.},
journal ={EMBO reports},
volume={},
pages={null--null},
year=2019
}

Nicolai Wagner, Milena Schuhmacher, Annett Lohmann, André Nadler
A coumarin triflate reagent enables one-step synthesis of photo-caged lipid metabolites for studying cell signaling.
Chemistry, Art. No. doi: 10.1002/chem.201903909 (2019)
PubMed Source

Photorelease of caged compounds is among the most powerful experimental approaches for studying cellular functions on fast timescales. However, its full potential has yet to be exploited, as the number of caged small molecules available for cell biological studies has been limited by synthetic challenges. Addressing this problem, we developed a straightforward, one-step procedure for efficiently synthesizing caged compounds. We used an in situ generated benzylic coumarin triflate reagent to specifically functionalize carboxylate and phosphate moieties in the presence of free hydroxy groups and generated various caged lipid metabolites, including a number of GPCR ligands. By combining the photo-caged ligands with the respective receptors, we developed an easily implementable experimental platform for the optical control and analysis of GPCR-mediated signal transduction in living cells. Ultimately, the described synthetic strategy allows rapid generation of photo-caged small molecules and thus greatly facilitates the analysis of their biological roles in live cell microscopy assays.

@article{Wagner7509,
author={Nicolai Wagner, Milena Schuhmacher, Annett Lohmann, André Nadler},
title={A coumarin triflate reagent enables one-step synthesis of photo-caged lipid metabolites for studying cell signaling.},
journal ={Chemistry (Weinheim an der Bergstrasse, Germany)},
volume={},
pages={1--1},
year=2019
}

Karin D Prummel, Christopher Hess, Susan Nieuwenhuize, Hugo J Parker, Katherine W Rogers, Iryna Kozmikova, Claudia Racioppi, Eline C Brombacher, Anna Czarkwiani, Dunja Knapp, Sibylle Burger, Elena Chiavacci, Gopi Shah, Alexa Burger, Jan Huisken, Maximina H Yun, Lionel Christiaen, Zbynek Kozmik, Patrick Müller, Marianne Bronner, Robb Krumlauf, Christian Mosimann
A conserved regulatory program initiates lateral plate mesoderm emergence across chordates.
Nat Commun, 10(1) Art. No. 3857 (2019)
PubMed Source

Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolate a pan-LPM enhancer in the zebrafish-specific draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captures the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncover specific activity of zebrafish-derived drl reporters in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.

@article{Prummel7507,
author={Karin D Prummel, Christopher Hess, Susan Nieuwenhuize, Hugo J Parker, Katherine W Rogers, Iryna Kozmikova, Claudia Racioppi, Eline C Brombacher, Anna Czarkwiani, Dunja Knapp, Sibylle Burger, Elena Chiavacci, Gopi Shah, Alexa Burger, Jan Huisken, Maximina H Yun, Lionel Christiaen, Zbynek Kozmik, Patrick Müller, Marianne Bronner, Robb Krumlauf, Christian Mosimann},
title={A conserved regulatory program initiates lateral plate mesoderm emergence across chordates.},
journal ={Nature communications},
volume={10},
issue ={1},
pages={null--null},
year=2019
}

Sadjad Arzash, Patrick M McCall, Jingchen Feng, Margaret L Gardel, Fred C MacKintosh
Stress relaxation in F-actin solutions by severing.
Soft Matter, 15(31) 6300-6307 (2019)
PubMed Source

Networks of filamentous actin (F-actin) are important for the mechanics of most animal cells. These cytoskeletal networks are highly dynamic, with a variety of actin-associated proteins that control cross-linking, polymerization and force generation in the cytoskeleton. Inspired by recent rheological experiments on reconstituted solutions of dynamic actin filaments, we report a theoretical model that describes stress relaxation behavior of these solutions in the presence of severing proteins. We show that depending on the kinetic rates of assembly, disassembly, and severing, one can observe both length-dependent and length-independent relaxation behavior.

@article{Arzash7502,
author={Sadjad Arzash, Patrick M McCall, Jingchen Feng, Margaret L Gardel, Fred C MacKintosh},
title={Stress relaxation in F-actin solutions by severing.},
journal ={Soft matter},
volume={15},
issue ={31},
pages={6300--6307},
year=2019
}

Clyde Savio Pinto, Ameya Khandekar, Rajasekaran Bhavna, Petra Kiesel, Gaia Pigino, Mahendra Sonawane
Microridges are apical epithelial projections formed of F-actin networks that organize the glycan layer.
Sci Rep, 9(1) Art. No. 12191 (2019)
PubMed Source

Apical projections are integral functional units of epithelial cells. Microvilli and stereocilia are cylindrical apical projections that are formed of bundled actin. Microridges on the other hand, extend laterally, forming labyrinthine patterns on surfaces of various kinds of squamous epithelial cells. So far, the structural organization and functions of microridges have remained elusive. We have analyzed microridges on zebrafish epidermal cells using confocal and electron microscopy methods including electron tomography, to show that microridges are formed of F-actin networks and require the function of the Arp2/3 complex for their maintenance. During development, microridges begin as F-actin punctae showing signatures of branching and requiring an active Arp2/3 complex. Using inhibitors of actin polymerization and the Arp2/3 complex, we show that microridges organize the surface glycan layer. Our analyses have unraveled the F-actin organization supporting the most abundant and evolutionarily conserved apical projection, which functions in glycan organization.

@article{Pinto7501,
author={Clyde Savio Pinto, Ameya Khandekar, Rajasekaran Bhavna, Petra Kiesel, Gaia Pigino, Mahendra Sonawane},
title={Microridges are apical epithelial projections formed of F-actin networks that organize the glycan layer.},
journal ={Scientific reports},
volume={9},
issue ={1},
pages={null--null},
year=2019
}