Developmental biology

  • Article
    | Open Access

    The BEN-solo proteins—including Insensitive (Insv), Elba1 and Elba2—function in both transcriptional repression and chromatin insulation. Here, the authors investigate the role of these proteins in Drosophila embryos, finding that ELBA and Insv function as general insulators and partition active chromatin to ensure proper gene activation in Drosophila.

    • Malin Ueberschär
    • , Huazhen Wang
    • , Chun Zhang
    • , Shu Kondo
    • , Tsutomu Aoki
    • , Paul Schedl
    • , Eric C. Lai
    • , Jiayu Wen
    •  & Qi Dai
  • Article
    | Open Access

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.

    • Osamu Iwasaki
    • , Hideki Tanizawa
    • , Kyoung-Dong Kim
    • , Andrew Kossenkov
    • , Timothy Nacarelli
    • , Sanki Tashiro
    • , Sonali Majumdar
    • , Louise C. Showe
    • , Rugang Zhang
    •  & Ken-ichi Noma
  • Article
    | Open Access

    Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.

    • Giovanni Giuseppe Giobbe
    • , Claire Crowley
    • , Camilla Luni
    • , Sara Campinoti
    • , Moustafa Khedr
    • , Kai Kretzschmar
    • , Martina Maria De Santis
    • , Elisa Zambaiti
    • , Federica Michielin
    • , Laween Meran
    • , Qianjiang Hu
    • , Gijs van Son
    • , Luca Urbani
    • , Anna Manfredi
    • , Monica Giomo
    • , Simon Eaton
    • , Davide Cacchiarelli
    • , Vivian S. W. Li
    • , Hans Clevers
    • , Paola Bonfanti
    • , Nicola Elvassore
    •  & Paolo De Coppi
  • Article
    | Open Access

    Most cases of autosomal dominant polycystic kidney disease (ADPKD) are due to mutations in PKD1. Here, Tsukiyama et al. generate monkeys with mutations in PKD1 and show that animals recapitulate key pathological features of the human disease, suggesting these may provide insights into ADPKD pathogenesis and contribute to the development of future therapeutic strategies.

    • Tomoyuki Tsukiyama
    • , Kenichi Kobayashi
    • , Masataka Nakaya
    • , Chizuru Iwatani
    • , Yasunari Seita
    • , Hideaki Tsuchiya
    • , Jun Matsushita
    • , Kahoru Kitajima
    • , Ikuo Kawamoto
    • , Takahiro Nakagawa
    • , Koji Fukuda
    • , Teppei Iwakiri
    • , Hiroyuki Izumi
    • , Iori Itagaki
    • , Shinji Kume
    • , Hiroshi Maegawa
    • , Ryuichi Nishinakamura
    • , Saori Nishio
    • , Shinichiro Nakamura
    • , Akihiro Kawauchi
    •  & Masatsugu Ema
  • Article
    | Open Access

    XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X chromosome inactivation. Here, the authors investigate TEs associated with the XACT locus and identify a critical enhancer for its regulation, which evolved from an ancestral group of mammalian endogenous retroviruses, prior to the emergence of XACT.

    • Miguel Casanova
    • , Madeleine Moscatelli
    • , Louis Édouard Chauvière
    • , Christophe Huret
    • , Julia Samson
    • , Tharvesh Moideen Liyakat Ali
    • , Olga Rosspopoff
    •  & Claire Rougeulle
  • Article
    | Open Access

    Ageing is associated with clonal hematopoiesis of indeterminate potential (CHIP), which is linked to increased risks of hematological malignancies. Here the authors uncover an epigenetic mechanism through which mutant p53 drives clonal hematopoiesis through interaction with EZH2.

    • Sisi Chen
    • , Qiang Wang
    • , Hao Yu
    • , Maegan L. Capitano
    • , Sasidhar Vemula
    • , Sarah C. Nabinger
    • , Rui Gao
    • , Chonghua Yao
    • , Michihiro Kobayashi
    • , Zhuangzhuang Geng
    • , Aidan Fahey
    • , Danielle Henley
    • , Stephen Z. Liu
    • , Sergio Barajas
    • , Wenjie Cai
    • , Eric R. Wolf
    • , Baskar Ramdas
    • , Zhigang Cai
    • , Hongyu Gao
    • , Na Luo
    • , Yang Sun
    • , Terrence N. Wong
    • , Daniel C. Link
    • , Yunlong Liu
    • , H. Scott Boswell
    • , Lindsey D. Mayo
    • , Gang Huang
    • , Reuben Kapur
    • , Mervin C. Yoder
    • , Hal E. Broxmeyer
    • , Zhonghua Gao
    •  & Yan Liu
  • Article
    | Open Access

    Stem-cell-specific genes regulate processes such as maintenance, identity and/or division. Here, the authors show that in the Arabidopsis root TCX2, a gene expressed across different stem cell populations (a stem-cell-ubiquitous gene), controls division and identity by regulating stem-cell-type-specific networks.

    • Natalie M. Clark
    • , Eli Buckner
    • , Adam P. Fisher
    • , Emily C. Nelson
    • , Thomas T. Nguyen
    • , Abigail R. Simmons
    • , Maria A. de Luis Balaguer
    • , Tiara Butler-Smith
    • , Parnell J. Sheldon
    • , Dominique C. Bergmann
    • , Cranos M. Williams
    •  & Rossangela Sozzani
  • Article
    | Open Access

    Senescence of metabolically active cells is a process linked to ageing. Here the authors reveal that CSB is required to block replicative senescence, and epigenetic control of CSB downregulation triggers proliferative arrest in a p21-dependent manner.

    • Clément Crochemore
    • , Cristina Fernández-Molina
    • , Benjamin Montagne
    • , Audrey Salles
    •  & Miria Ricchetti
  • Article
    | Open Access

    How a precancerous form (dysplasia) becomes gastric cancer is unclear. Here, the authors assess the role of Kras activation in heterogenous dysplastic cells in murine stomach corpus organoids, identifying two dysplastic stem cell populations and show that MEK inhibition causes alterations in cell behavior.

    • Jimin Min
    • , Paige N. Vega
    • , Amy C. Engevik
    • , Janice A. Williams
    • , Qing Yang
    • , Loraine M. Patterson
    • , Alan J. Simmons
    • , R. Jarrett Bliton
    • , Joshua W. Betts
    • , Ken S. Lau
    • , Scott T. Magness
    • , James R. Goldenring
    •  & Eunyoung Choi
  • Article
    | Open Access

    The adult mammalian inner ear cells cannot regenerate nor proliferate. Here, the authors show that co-activation of Myc and NOTCH pathways can stimulate proliferation of inner ear sensory epithelial cells, which can be induced to become hair cell-like cells in vitro and in vivo.

    • Yilai Shu
    • , Wenyan Li
    • , Mingqian Huang
    • , Yi-Zhou Quan
    • , Deborah Scheffer
    • , Chunjie Tian
    • , Yong Tao
    • , Xuezhong Liu
    • , Konrad Hochedlinger
    • , Artur A. Indzhykulian
    • , Zhengmin Wang
    • , Huawei Li
    •  & Zheng-Yi Chen
  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    • , Yongge Zhao
    • , Mina O. Seedhom
    • , Christelle Harly
    • , Izumi Ohigashi
    • , Michael Kelly
    • , Yousuke Takahama
    • , Jonathan W. Yewdell
    • , Maggie Cam
    •  & Avinash Bhandoola
  • Article
    | Open Access

    One of the underlying causes of aging is the accumulation of senescent cells, but their turnover rates and dynamics during ageing are unknown. Here the authors measure and model senescent cell production and removal and explore implications for mortality.

    • Omer Karin
    • , Amit Agrawal
    • , Ziv Porat
    • , Valery Krizhanovsky
    •  & Uri Alon
  • Article
    | Open Access

    How reproducible human kidney organoids derived from different iPSC lines are, and how faithful they are to human kidney tissue remain unclear. Here, the authors use four human iPSC lines to derive kidney organoids and show how organoid composition is reproducible, comparable to human tissue and of improved quality after transplantation.

    • Ayshwarya Subramanian
    • , Eriene-Heidi Sidhom
    • , Maheswarareddy Emani
    • , Katherine Vernon
    • , Nareh Sahakian
    • , Yiming Zhou
    • , Maria Kost-Alimova
    • , Michal Slyper
    • , Julia Waldman
    • , Danielle Dionne
    • , Lan T. Nguyen
    • , Astrid Weins
    • , Jamie L. Marshall
    • , Orit Rosenblatt-Rosen
    • , Aviv Regev
    •  & Anna Greka
  • Article
    | Open Access

    Inducible genome editing systems often suffer from leakiness or reduced activity. Here the authors develop CRISPR-Switch, a Cre recombinase ON/OFF-controlled sgRNA cassette that allows consecutive editing of two loci.

    • Krzysztof Chylinski
    • , Maria Hubmann
    • , Ruth E. Hanna
    • , Connor Yanchus
    • , Georg Michlits
    • , Esther C. H. Uijttewaal
    • , John Doench
    • , Daniel Schramek
    •  & Ulrich Elling
  • Article
    | Open Access

    Songbirds have extensive germline–soma genome differences due to developmental elimination of a germline-specific chromosome (GRC). Here, the authors show that the GRC contains dozens of expressed developmental genes, some of which have been on the GRC since the ancestor of all songbirds.

    • Cormac M. Kinsella
    • , Francisco J. Ruiz-Ruano
    • , Anne-Marie Dion-Côté
    • , Alexander J. Charles
    • , Toni I. Gossmann
    • , Josefa Cabrero
    • , Dennis Kappei
    • , Nicola Hemmings
    • , Mirre J. P. Simons
    • , Juan Pedro M. Camacho
    • , Wolfgang Forstmeier
    •  & Alexander Suh
  • Article
    | Open Access

    It remains unclear why quiescent neural stem cells (qNSCs) in the subventricular zone of the mouse brain have enlarged lysosomes. Here, authors demonstrate that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs, which prevents the NSC exit from quiescence.

    • Taeko Kobayashi
    • , Wenhui Piao
    • , Toshiya Takamura
    • , Hiroshi Kori
    • , Hitoshi Miyachi
    • , Satsuki Kitano
    • , Yumiko Iwamoto
    • , Mayumi Yamada
    • , Itaru Imayoshi
    • , Seiji Shioda
    • , Andrea Ballabio
    •  & Ryoichiro Kageyama
  • Article
    | Open Access

    The scaffold protein Scribble (Scrib) has roles in PCP and tight junction formation. Here the authors show that during embryo implantation in mouse, Scrib is needed to form the avascular primary decidual zone by transforming stromal cells into an epithelial cell-like barrier around the crypt, protecting the embryo from harmful infiltrations.

    • Jia Yuan
    • , Shizu Aikawa
    • , Wenbo Deng
    • , Amanda Bartos
    • , Gerd Walz
    • , Florian Grahammer
    • , Tobias B. Huber
    • , Xiaofei Sun
    •  & Sudhansu K. Dey
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Article
    | Open Access

    Uterine gland development is essential for successful embryo implantation, decidua formation and placental development. Here the authors demonstrate that neonatal Wnt-dependent Lgr5 expressing stem/progenitor cells at the tips of developing glands are indispensable for uterine gland development.

    • Ryo Seishima
    • , Carly Leung
    • , Swathi Yada
    • , Katzrin Bte Ahmed Murad
    • , Liang Thing Tan
    • , Amin Hajamohideen
    • , Si Hui Tan
    • , Hideki Itoh
    • , Kazuhiro Murakami
    • , Yoshihiro Ishida
    • , Satoshi Nakamizo
    • , Yusuke Yoshikawa
    • , Esther Wong
    •  & Nick Barker
  • Article
    | Open Access

    Integrin-linked kinase (ILK) is an important mediator of integrin signaling. Here Park et al. show that mice with endothelial-specific deletion of Ilk develop vascular defects that resemble familial exudative vitreoretinopathy, and identify mutations in ILK in patients with exudative vitreoretinopathy suggesting a potential role in human pathogenesis.

    • Hongryeol Park
    • , Hiroyuki Yamamoto
    • , Lucas Mohn
    • , Lea Ambühl
    • , Kenichi Kanai
    • , Inga Schmidt
    • , Kee-Pyo Kim
    • , Alessia Fraccaroli
    • , Silke Feil
    • , Harald J. Junge
    • , Eloi Montanez
    • , Wolfgang Berger
    •  & Ralf H. Adams
  • Article
    | Open Access

    The hepatopancreatic ductal (HPD) system connects both liver and pancreas to the intestine but the molecular details of HPD development are unclear. Here, the authors describe how regionalised Eph/Ephrin signaling regulates HPD morphogenesis by promoting cellular rearrangements leading to an open tube.

    • M. Ilcim Thestrup
    • , Sara Caviglia
    • , Jordi Cayuso
    • , Ronja L. S. Heyne
    • , Racha Ahmad
    • , Wolfgang Hofmeister
    • , Letizia Satriano
    • , David G. Wilkinson
    • , Jesper B. Andersen
    •  & Elke A. Ober
  • Article
    | Open Access

    Glutamatergic neurons in the mammalian cortex are born from a heterogeneous pool of embryonic progenitors, however, it is unclear how these different progenitors contribute to diversity within the mature cortex. In this study, authors combine in utero progenitor labeling techniques with targeted Patch-Seq methods and high resolution synaptic circuit mapping in the mature mouse cortex to show that intermediate progenitors can generate restricted sets of transcriptomically-defined glutamatergic neurons that have distinct patterns of local and long-range synaptic connections.

    • Tommas J. Ellender
    • , Sophie V. Avery
    • , Kashif Mahfooz
    • , Jakub Scaber
    • , Alexander von Klemperer
    • , Sophie L. Nixon
    • , Matthew J. Buchan
    • , Joram J. van Rheede
    • , Aleksandra Gatti
    • , Cameron Waites
    • , Hania J. Pavlou
    • , David Sims
    • , Sarah E. Newey
    •  & Colin J. Akerman
  • Article
    | Open Access

    There is limited knowledge of markers to identify various waves of murine embryonic hematopoiesis. Here, the authors show that the expression of toll-like receptor 2 (TLR2) on E7.5 c-kit+ cells marks the emergence of erythro-myeloid progenitor precursors and that the Tlr2 locus is active in E8.5 precursors of adult HSCs.

    • Jana Balounová
    • , Iva Šplíchalová
    • , Martina Dobešová
    • , Michal Kolář
    • , Karel Fišer
    • , Jan Procházka
    • , Radislav Sedlacek
    • , Andrea Jurisicova
    • , Hoon-ki Sung
    • , Vladimír Kořínek
    • , Meritxell Alberich-Jorda
    • , Isabelle Godin
    •  & Dominik Filipp
  • Article
    | Open Access

    Spermatogonial stem cells have the dual capacity to self-renew and differentiate into mature spermatozoa. Here, using transcriptome analyses of juvenile testes in gene-edited mice, the authors demonstrate that PRAMEF12 is required to maintain germ cell homeostasis and promote their differentiation.

    • Zhengpin Wang
    • , Xiaojiang Xu
    • , Jian-Liang Li
    • , Cameron Palmer
    • , Dragan Maric
    •  & Jurrien Dean
  • Article
    | Open Access

    The contribution of long-range signaling to cortical gyrification remains poorly understood. In this study, authors demonstrate that the combined genetic loss of transcription factors Lmx1a and Lmx1b, expressed in the telencephalic dorsal midline neuroepithelium and head mesenchyme, respectively, induces gyrification in the mouse neocortex

    • Victor V. Chizhikov
    • , Igor Y. Iskusnykh
    • , Ekaterina Y. Steshina
    • , Nikolai Fattakhov
    • , Anne G. Lindgren
    • , Ashwin S. Shetty
    • , Achira Roy
    • , Shubha Tole
    •  & Kathleen J. Millen
  • Article
    | Open Access

    LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

    • Jordan P. Lewandowski
    • , James C. Lee
    • , Taeyoung Hwang
    • , Hongjae Sunwoo
    • , Jill M. Goldstein
    • , Abigail F. Groff
    • , Nydia P. Chang
    • , William Mallard
    • , Adam Williams
    • , Jorge Henao-Meija
    • , Richard A. Flavell
    • , Jeannie T. Lee
    • , Chiara Gerhardinger
    • , Amy J. Wagers
    •  & John L. Rinn
  • Article
    | Open Access

    Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.

    • Roxsan Manshouri
    • , Etienne Coyaud
    • , Samrat T. Kundu
    • , David H. Peng
    • , Sabrina A. Stratton
    • , Kendra Alton
    • , Rakhee Bajaj
    • , Jared J. Fradette
    • , Rosalba Minelli
    • , Michael D. Peoples
    • , Alessandro Carugo
    • , Fengju Chen
    • , Christopher Bristow
    • , Jeffrey J. Kovacs
    • , Michelle C. Barton
    • , Tim Heffernan
    • , Chad J. Creighton
    • , Brian Raught
    •  & Don L. Gibbons
  • Article
    | Open Access

    EMT is a developmental process that is aberrantly activated in metastasizing cancer cells, but how multiple transcription factors regulate EMT is unclear. Here, the authors uncover a gene regulatory network between Prrx1 and Snail1 that selects EMT mode in developing vertebrates and cancer cells.

    • Hassan Fazilaty
    • , Luciano Rago
    • , Khalil Kass Youssef
    • , Oscar H. Ocaña
    • , Francisco Garcia-Asencio
    • , Aida Arcas
    • , Juan Galceran
    •  & M. Angela Nieto
  • Article
    | Open Access

    Proper ovarian differentiation requires RUNX1. Here, the authors show that double knockout of Runx1/Foxl2 results in masculinization of fetal ovaries, and that RUNX1 and FOXL2 jointly occupy common chromatin regions to maintain pre-granulosa cell identity in the fetal ovary.

    • Barbara Nicol
    • , Sara A. Grimm
    • , Frédéric Chalmel
    • , Estelle Lecluze
    • , Maëlle Pannetier
    • , Eric Pailhoux
    • , Elodie Dupin-De-Beyssat
    • , Yann Guiguen
    • , Blanche Capel
    •  & Humphrey H.-C. Yao
  • Article
    | Open Access

    C. elegans is a commonly used model organism in the study of ageing, and differences in genetic background can result in varying strain longevity. Here the authors demonstrate that a background mutation in fln-2 affects life-limiting pharyngeal infection and that in the mutant background the beneficial effect of sir-2.1 over-expression is suppressed.

    • Yuan Zhao
    • , Hongyuan Wang
    • , Richard J. Poole
    •  & David Gems
  • Article
    | Open Access

    Beta3-adrenergic receptor (b3-AR) signaling in response to cold activates adipose tissue thermogenesis. Here the authors identify the transcription factor FoxP1 as a direct negative regulator of b3-AR expression and show that loss of FoxP1 leads to enhanced development of thermogenic adipose tissue.

    • Pei Liu
    • , Sixia Huang
    • , Shifeng Ling
    • , Shuqin Xu
    • , Fuhua Wang
    • , Wei Zhang
    • , Rujiang Zhou
    • , Lin He
    • , Xuechun Xia
    • , Zhengju Yao
    • , Ying Fan
    • , Niansong Wang
    • , Congxia Hu
    • , Xiaodong Zhao
    • , Haley O. Tucker
    • , Jiqiu Wang
    •  & Xizhi Guo
  • Article
    | Open Access

    Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

    • Iuliia O. Peshkova
    • , Turan Aghayev
    • , Aliia R. Fatkhullina
    • , Petr Makhov
    • , Elizaveta K. Titerina
    • , Satoru Eguchi
    • , Yin Fei Tan
    • , Andrew V. Kossenkov
    • , Marina V. Khoreva
    • , Lyudmila V. Gankovskaya
    • , Stephen M. Sykes
    •  & Ekaterina K. Koltsova
  • Article
    | Open Access

    Currently, few mouse models exist to recapitulate human melanomagenesis. Here, the authors establish a c-Kit-CreER-driven model to target melanocyte stem cells (McSCs) and show that oncogenic McSCs give rise to epidermal melanoma that invade into the dermis, similar to human melanoma.

    • Qi Sun
    • , Wendy Lee
    • , Yasuaki Mohri
    • , Makoto Takeo
    • , Chae Ho Lim
    • , Xiaowei Xu
    • , Peggy Myung
    • , Radhika P. Atit
    • , M. Mark Taketo
    • , Rana S. Moubarak
    • , Markus Schober
    • , Iman Osman
    • , Denise L. Gay
    • , Dieter Saur
    • , Emi K. Nishimura
    •  & Mayumi Ito
  • Article
    | Open Access

    The development of post-chemotherapy resistance is a significant issue in the management of AML. Here, Caiado et al. suggest that the issue might be circumvented via upfront combination with hypomethylating agents that shape the clonal dynamics and transcriptional landscape of relapsing AML

    • Francisco Caiado
    • , Diogo Maia-Silva
    • , Carolina Jardim
    • , Nina Schmolka
    • , Tânia Carvalho
    • , Cláudia Reforço
    • , Rita Faria
    • , Branka Kolundzija
    • , André E. Simões
    • , Tuncay Baubec
    • , Christopher R. Vakoc
    • , Maria Gomes da Silva
    • , Markus G. Manz
    • , Ton N. Schumacher
    • , Håkan Norell
    •  & Bruno Silva-Santos
  • Article
    | Open Access

    In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation

    • Rachel Eyre
    • , Denis G. Alférez
    • , Angélica Santiago-Gómez
    • , Kath Spence
    • , James C. McConnell
    • , Claire Hart
    • , Bruno M. Simões
    • , Diane Lefley
    • , Claudia Tulotta
    • , Joanna Storer
    • , Austin Gurney
    • , Noel Clarke
    • , Mick Brown
    • , Sacha J. Howell
    • , Andrew H. Sims
    • , Gillian Farnie
    • , Penelope D. Ottewell
    •  & Robert B. Clarke
  • Article
    | Open Access

    The endothelium actively maintains an anticoagulant surface through expression of thrombomodulin. Here, Peghaire et al. identify an anti-thrombotic pathway that controls thrombomodulin expression selectively in regions of low shear stress, via cooperation of the transcription factors ERG and KLF2.

    • C. Peghaire
    • , N. P. Dufton
    • , M. Lang
    • , I. I. Salles-Crawley
    • , J. Ahnström
    • , V. Kalna
    • , C. Raimondi
    • , C. Pericleous
    • , L. Inuabasi
    • , R. Kiseleva
    • , V. R. Muzykantov
    • , J. C. Mason
    • , G. M. Birdsey
    •  & A. M. Randi
  • Article
    | Open Access

    The ovary is covered by a surface epithelium (OSE) and cells mediating its repair post ovulation are unclear. Here, the authors identify the Protein C Receptor (Procr) as marking progenitor cells, distinct from Lgr5+ stem cells, on the murine surface epithelium that repair the OSE post ovulation.

    • Jingqiang Wang
    • , Daisong Wang
    • , Kun Chu
    • , Wen Li
    •  & Yi Arial Zeng
  • Article
    | Open Access

    The 302-neuron connectome of the nematode C. elegans has been completely mapped, yet the design principles that explain how the connectome structure determines its function are unknown. Here, the authors show that physical principles of symmetry and mathematical tools of symmetry groups can be used to understand C. elegans neural locomotion circuits.

    • Flaviano Morone
    •  & Hernán A. Makse
  • Article
    | Open Access

    Vertebrate telencephalon formation requires Foxg-Fgf8 cross-regulation, but while ascidians express Foxg in the neural plate, they lack a telencephalon. Here the authors show that Foxg loss does not affect ascidian brain formation, indicating that telencephalon evolution required recruitment of Fgf downstream of Foxg.

    • Boqi Liu
    •  & Yutaka Satou
  • Article
    | Open Access

    Hydralazine is a drug used in the treatment of heart failure and cancer, and it has recently been shown to promote lifespan in C. elegans. Here, the authors elucidate the mechanism of action of hydralazine, and show that it targets PKA to promote mitochondrial function via Sirtuin1/5.

    • Esmaeil Dehghan
    • , Mohammad Goodarzi
    • , Bahar Saremi
    • , Rueyling Lin
    •  & Hamid Mirzaei
  • Article
    | Open Access

    Mapping transcription factors (TFs) occupancy is essential for understanding transcriptional programs. Here the authors use biotinylated knockin alleles of key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to map their genome-wide occupancy in the fetal and adult mouse heart, providing insight into the cardiac transcriptional regulatory network.

    • Brynn N. Akerberg
    • , Fei Gu
    • , Nathan J. VanDusen
    • , Xiaoran Zhang
    • , Rui Dong
    • , Kai Li
    • , Bing Zhang
    • , Bin Zhou
    • , Isha Sethi
    • , Qing Ma
    • , Lauren Wasson
    • , Tong Wen
    • , Jinhua Liu
    • , Kunzhe Dong
    • , Frank L. Conlon
    • , Jiliang Zhou
    • , Guo-Cheng Yuan
    • , Pingzhu Zhou
    •  & William T. Pu
  • Article
    | Open Access

    DNA repair by microhomology-mediated end joining creates precise deletions based on flanking microhomologies. Here the authors use CRISPR-Cas9 to recreate pathogenic deletion mutations using existing microhomologies in the human genome identified by their program MHcut.

    • Janin Grajcarek
    • , Jean Monlong
    • , Yoko Nishinaka-Arai
    • , Michiko Nakamura
    • , Miki Nagai
    • , Shiori Matsuo
    • , David Lougheed
    • , Hidetoshi Sakurai
    • , Megumu K. Saito
    • , Guillaume Bourque
    •  & Knut Woltjen
  • Article
    | Open Access

    Decreased autophagy is a hallmark of ageing, but its inter-tissue regulation is poorly understood. Here, Zhou et al. identify mir-83 in C. elegans, which is transported across tissues and suppresses autophagy, contributing to age-related decline.

    • Yifei Zhou
    • , Xueqing Wang
    • , Mengjiao Song
    • , Zhidong He
    • , Guizhong Cui
    • , Guangdun Peng
    • , Christoph Dieterich
    • , Adam Antebi
    • , Naihe Jing
    •  & Yidong Shen
  • Article
    | Open Access

    Spinal interneurons (IN) coordinate motoneuron activity to modulate locomotion behavior. Here, the authors characterize a subset of IN subtypes expressing the Maf transcription factor Traffic Jam (TJ) and report the distinct effects of their activation on body posture and locomotion in Drosophila larvae.

    • H. Babski
    • , T. Jovanic
    • , C. Surel
    • , S. Yoshikawa
    • , M. F Zwart
    • , J. Valmier
    • , J. B. Thomas
    • , J. Enriquez
    • , P. Carroll
    •  & A. Garcès
  • Article
    | Open Access

    Senolytic compounds have the ability to eliminate senescent cells from tissues and have been shown to be beneficial in various animal models of age-related diseases. Here the authors show that cardiac glycosides commonly used for heart diseases have senolytic properties in humanized mouse models of tumorigenesis and lung fibrosis.

    • Francisco Triana-Martínez
    • , Pilar Picallos-Rabina
    • , Sabela Da Silva-Álvarez
    • , Federico Pietrocola
    • , Susana Llanos
    • , Verónica Rodilla
    • , Enrica Soprano
    • , Pablo Pedrosa
    • , Alba Ferreirós
    • , Marta Barradas
    • , Fernanda Hernández-González
    • , Marta Lalinde
    • , Neus Prats
    • , Cristina Bernadó
    • , Patricia González
    • , María Gómez
    • , Maria P. Ikonomopoulou
    • , Pablo J. Fernández-Marcos
    • , Tomás García-Caballero
    • , Pablo del Pino
    • , Joaquín Arribas
    • , Anxo Vidal
    • , Miguel González-Barcia
    • , Manuel Serrano
    • , María I. Loza
    • , Eduardo Domínguez
    •  & Manuel Collado
  • Article
    | Open Access

    Trophectoderm lineage development is essential for implantation, placentation, and healthy pregnancy. Here the authors map super-enhancers (SEs) in trophoblast stem cells and find both TE-specific master regulators and 150 previous uncharacterised transcription factors that are SE-associated, providing insight into trophectoderm-specific regulatory networks.

    • Bum-Kyu Lee
    • , Yu jin Jang
    • , Mijeong Kim
    • , Lucy LeBlanc
    • , Catherine Rhee
    • , Jiwoon Lee
    • , Samuel Beck
    • , Wenwen Shen
    •  & Jonghwan Kim
  • Article
    | Open Access

    Previous gene editing in haematopoietic stem cells (HSCs) has focussed on a heterogeneous CD34+ population. Here, the authors demonstrate high efficiency CRISPR/Cas9-based editing of purified long-term HSCs using non-homologous end joining and homology-directed repair, by directing isoform-specific expression of GATA1.

    • Elvin Wagenblast
    • , Maria Azkanaz
    • , Sabrina A. Smith
    • , Lorien Shakib
    • , Jessica L. McLeod
    • , Gabriela Krivdova
    • , Joana Araújo
    • , Leonard D. Shultz
    • , Olga I. Gan
    • , John E. Dick
    •  & Eric R. Lechman
  • Article
    | Open Access

    Pluripotent stem cell colonies are encircled by large cornerstone focal adhesions (FAs). Here, using super-resolution imaging, the authors describe features in the nanoscale makeup of these stable FAs such as inverted vinculin, lateral talin segregation and distinct kank protein distributions.

    • Aki Stubb
    • , Camilo Guzmán
    • , Elisa Närvä
    • , Jesse Aaron
    • , Teng-Leong Chew
    • , Markku Saari
    • , Mitro Miihkinen
    • , Guillaume Jacquemet
    •  & Johanna Ivaska