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TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry
How RNA polymerase II subunits enter the nucleus is not well understood. Here, the authors show that Transport and Golgi organization protein 6, TANGO6, recruits RNA polymerase II subunit B2, RPB2, to the ER membrane in a retrograde manner and transports it to the nucleus with the aid of importins.
- Zhi Feng
- , Shengnan Liu
- & Li Li
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A distinct Acyl-CoA binding protein (ACBP6) shapes tissue plasticity during nutrient adaptation in Drosophila
Plasticity in tissue function and morphology is shaped by adaptive responses to nutrient changes. Here, the authors found that a putative calibration of acyl-CoA and acetyl-CoA metabolism through ACBP6 is crucial for Drosophila intestine’s proliferative homeostasis in response to nutrient changes.
- Xiaotong Li
- & Jason Karpac
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Prolonging somatic cell proliferation through constitutive hox gene expression in C. elegans
Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.
- Svenia D. Heinze
- , Simon Berger
- & Alex Hajnal
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Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation
Cardiac regeneration is hindered by the limited division of cardiomyocytes. Here, the authors show that Arid1a drives maturation and limits proliferation through interaction with Yap. Suppression of Arid1a enhances proliferation after injury.
- Cornelis J. Boogerd
- , Ilaria Perini
- & Eva van Rooij
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A highly sensitive strategy for monitoring real-time proliferation of targeted cell types in vivo
Currently, tracking cell proliferation in vivo is hard. Here the authors report a method where the time series of proliferation of targeted cell types can be monitored in vivo in the same individuals, with no need for animal sacrifice: they use this to assess β-cell and hepatocyte proliferation in mice.
- Hiroto Sugawara
- , Junta Imai
- & Hideki Katagiri
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ACL and HAT1 form a nuclear module to acetylate histone H4K5 and promote cell proliferation
Xu et al. showed that a histone acetyltransferase interacts with an acetyl-CoA synthetic enzyme for histone acetylation to stimulate gene expression and endosperm cell division, pointing to a mechanism coupling energy metabolism to epigenetics.
- Qiutao Xu
- , Yaping Yue
- & Dao-Xiu Zhou
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Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice
Early lipid accumulation is thought to contribute to liver regeneration through unclear functional mechanisms. Here the authors identify an epigenetic regulator, MIER1, that bridges the acute lipid accumulation and cell cycle gene transcription during liver regeneration after surgical resection in male mice.
- Yanhao Chen
- , Lanlan Chen
- & Qiurong Ding
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Translation regulatory factor BZW1 regulates preimplantation embryo development and compaction by restricting global non-AUG Initiation
It is unclear how translational efficiency and codon stringency affect zygotic genome activation and early embryonic development. Here they show that the zygotic gene BZW1 increases start codon stringency, which is important for preimplantation development.
- Jue Zhang
- , Shuai-Bo Pi
- & Heng-Yu Fan
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Article
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Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes
T cell development involves extensive proliferation of developing thymocytes. Here, the authors demonstrate that the transcription factor Zfp335 regulates the survival post-β-selection thymocytes via the cGAS/STING pathway.
- Jeremy J. Ratiu
- , William E. Barclay
- & Yuan Zhuang
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Predictive model for cytoneme guidance in Hedgehog signaling based on Ihog- Glypicans interaction
Cytonemes are specialized filopodia-like structures known to be involved in signal transduction. Here they propose a new predictive model for cytoneme guidance in Hedgehog signaling, which is based on Ihog, Dally, and Dlp protein levels.
- Adrián Aguirre-Tamaral
- , Manuel Cambón
- & Isabel Guerrero
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A SOX17-PDGFB signaling axis regulates aortic root development
Little is known about the developmental causes of aortic root defects. Here the authors show that the inactivation of Sox17 in aortic root endothelium results in aortic root defects affecting aortic valve and coronary ostium.
- Pengfei Lu
- , Ping Wang
- & Bin Zhou
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Article
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A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
RNA polymerase III changes its subunit composition during mammalian development. Here the authors report that loss of subunit POLR3G, which re-emerges in cancer, promotes expression of small NF90-associated RNA (snaR-A), a noncoding RNA implicated in cell proliferation and metastasis.
- Kevin Van Bortle
- , David P. Marciano
- & Michael P. Snyder
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Activation of Nkx2.5 transcriptional program is required for adult myocardial repair
Cardiac developmental genes have been associated with regenerative potential. Here the authors identify a Nkx2.5-dependent gene regulatory network operating through ect2, psmb3, and psmd7 to orchestrate cell cycle re-entry, proteolysis, and mitochondrial metabolism during myocardial repair.
- Carmen de Sena-Tomás
- , Angelika G. Aleman
- & Kimara L. Targoff
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Metabolic control of progenitor cell propagation during Drosophila tracheal remodeling
Tracheal remodeling is a key step during Drosophila metamorphosis. Here they report that tracheal progenitor cells are activated through Yorkie-dependent proliferation and migration, which is induced by metabolic deficit and insulin signaling.
- Yue Li
- , Pengzhen Dong
- & Hai Huang
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Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle
The adult mammalian heart exhibits stubbornly low levels of cardiomyocyte proliferation, leading to high morbidity after injury or heart attack. Here the authors develop an approach for tracking cardiomyocyte cell cycling and show that the majority are located adjacent to the endocardium.
- Xiuxiu Liu
- , Wenjuan Pu
- & Bin Zhou
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Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver
Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.
- Chi Zhang
- , Filippo Macchi
- & Kirsten C. Sadler
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High proliferation and delamination during skin epidermal stratification
How the developing skin epidermis is transformed from a simple single-layered epithelium to a complex and stratified barrier is still an open question. Here, the authors provide a model based on high proliferation and delamination of the keratinocyte progenitors that support the stratification process.
- Mareike Damen
- , Lisa Wirtz
- & Hisham Bazzi
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Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues
Although Hippo signaling restricts regeneration in many mammalian organs, the pharmaceutical tools available to modulate the pathway have been limited. Here, the authors report a small molecule that may inhibit a key element in the Hippo cascade and may activate regenerative responses in several mammalian tissues.
- Nathaniel Kastan
- , Ksenia Gnedeva
- & A. J. Hudspeth
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Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals
Mucosal-associated invariant T (MAIT) cells are key in immunity and diseases, but how their effector polarization is controlled is still unclear. Here, the authors show that an IL-1β/IL-23/mTORC2 axis is essential for the induction of IL-17-producing MAIT17, while an IL-2/IL-15/mTORC1 axis is important for the homeostasis of IFN-γ-producing MAIT1.
- Huishan Tao
- , Yun Pan
- & Xiao-Ping Zhong
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Mechanochemical control of epidermal stem cell divisions by B-plexins
It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.
- Chen Jiang
- , Ahsan Javed
- & Thomas Worzfeld
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YAP1/TAZ drives ependymoma-like tumour formation in mice
YAP1 gene fusions are found in subgroups of paediatric ependymomas. Here the authors show that YAP1 activation in NeuroD6 positive neuronal precursor cells can induce ependymoma-like tumours in mice.
- Noreen Eder
- , Federico Roncaroli
- & Sila K. Ultanir
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CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion
During cell division, centrosomes duplicate and newly formed centrioles must undergo centriole-to-centrosome conversion, but the molecular details are unclear. Here, the authors report that the centriole microtubule-triplet 9-fold structure scaffolds pericentriolar proteins and permits the conversion of centrioles to fully functional centrosomes.
- Enrico S. Atorino
- , Shoji Hata
- & Elmar Schiebel
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Renewed proliferation in adult mouse cochlea and regeneration of hair cells
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
- & Zheng-Yi Chen
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Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways
Animals can adapt their body size to changing environments (e.g., temperature) but the underlying molecular mechanisms are unknown. Here, the authors show that temperature and the genetic factors insulin-like peptide receptor and FoxO determine size in Hydra via the conserved pathways (Wnt/TGF-β).
- Benedikt M. Mortzfeld
- , Jan Taubenheim
- & Thomas C. G. Bosch
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High mitogenic stimulation arrests angiogenesis
High mitogenic stimuli have been suggested to promote endothelial cell proliferation and sprouting during angiogenesis. Here Pontes-Quero et al., by interfering with levels of VEGF and Notch signalling in single endothelial cells in vivo, find that high mitogenic stimuli instead arrest angiogenesis due to a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21.
- Samuel Pontes-Quero
- , Macarena Fernández-Chacón
- & Rui Benedito
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Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation
The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival.
- Tomohito Izumi
- , Junta Imai
- & Hideki Katagiri
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Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium
Oestrogen receptors α (ERα) are expressed in a subset of mammary epithelial cells. Here, the authors identify cells with low-ERα protein levels and show that distinct cell populations have distinct requirements for the AF1 and AF2 domains of the ERα, and ERα acts in a biphasic manner dependent on developmental stage.
- Stéphanie Cagnet
- , Dalya Ataca
- & Cathrin Brisken
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Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion
c-Kit receptor–Kit ligand complex signaling is known to activate c-Kit and is essential for tissue development. Here, Buono et al. show that membrane-bound KitL signaling induces proliferation via CAML-Akt-CREB pathway activation, establishing a role for bidirectional signaling in tissue expansion.
- Mario Buono
- , Marie-Laëtitia Thézénas
- & Claus Nerlov
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A conserved HH-Gli1-Mycn network regulates heart regeneration from newt to human
Due to the limited proliferation capacity of adult mammalian cardiomyocytes, the human heart has negligible regenerative capacity after injury. Here the authors show that a Hedgehog-Gli1-Mycn signaling cascade regulates cardiomyocyte proliferation and cardiac regeneration from amphibians to mammals.
- Bhairab N. Singh
- , Naoko Koyano-Nakagawa
- & Daniel J. Garry
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Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
During mammary gland involution, the organ undergoes extensive remodeling. Here, the authors explore the role of mammary gland adipose tissue (mgWAT) in this process and demonstrate that adipocyte hypertrophy and lipid trafficking underlie mgWAT expansion and epithelial regression.
- Rachel K. Zwick
- , Michael C. Rudolph
- & Valerie Horsley
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A positive feedback loop bi-stably activates fibroblasts
Normal adult tissue fibroblasts can be activated during wound healing, pathologic fibrosis and in cancer stroma, but the regulatory network that controls its dynamics is unknown. Here the authors show that fibroblasts are activated by a positive feedback loop formed by Twist1, Prrx1, and Tenascin-C bi-stably.
- So-Young Yeo
- , Keun-Woo Lee
- & Seok-Hyung Kim
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Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis
At high cell density or when plated on soft matrix, YAP/TAZ are redistributed from the nucleus to the cytosol, becoming transcriptionally inactive. Here the authors show that at high cell density, autophagosome formation is impaired due to reduced YAP/TAZ-dependent transcription of actomyosin genes
- Mariana Pavel
- , Maurizio Renna
- & David C. Rubinsztein
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Immuno-detection by sequencing enables large-scale high-dimensional phenotyping in cells
Detecting proteins and post-translational modifications is important for drug screens, but the number of proteins measurable simultaneously is limited. Here the authors use antibodies tagged with DNA barcodes and high-throughput sequencing to detect up to 70 (phospho-)proteins in stem cells.
- Jessie A. G. van Buggenum
- , Jan P. Gerlach
- & Klaas W. Mulder
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Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
VEGF-C is a key regulator of lymphatic development. Here, Zhang et al. show that while complete loss of its receptor VEGFR3 results in vessel hypoplasia, mosaic loss of VEGFR3 leads to hyperplasia through induction of cell proliferation in neighboringnon-targeted cells, uncovering cell- and non-cell-autonomous roles for VEGFR3 during lymphatic vessel growth.
- Yan Zhang
- , Maria H. Ulvmar
- & Taija Mäkinen
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p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response
Mutations in the gene encoding iRHOM2 are associated with hyperproliferative epidermal disorders. Here, the authors show that iRHOM2 is a target gene of p63, that together they regulate inflammation, cell survival and response to oxidative stress, and inhibition of p63-iRHOM2 signalling with an antioxidant reduces epidermal inflammation.
- Paola Arcidiacono
- , Catherine M. Webb
- & Anissa Chikh
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Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
During early postnatal development in mammals, cardiomyocytes exit the cell cycle, losing their regenerative capacity. Here the authors show that, following myocardial infarction, loss of microRNA-128 promotes cardiomyocyte proliferation and cardiac regeneration in adult mice partly via enhancing the expression of the chromatin modifier SUZ12.
- Wei Huang
- , Yuliang Feng
- & Yigang Wang
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Replication confers β cell immaturity
Adult beta cells, which are highly specialised insulin-secreting cells, rarely replicate. Puri et al. demonstrate that beta cell proliferative capacity is inversely correlated with their functionality and differentiation state, by inducing proliferation of adult cells with ectopic overexpression of the cell cycle regulator c-Myc.
- Sapna Puri
- , Nilotpal Roy
- & Matthias Hebrok
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Article
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High-resolution spatiotemporal transcriptome mapping of tomato fruit development and ripening
Cell-type transcriptome profiling greatly elucidate organismal development. Here, the authors report a spatiotemporally resolved comprehensive transcriptome analysis of tomato fruit ontogeny and suggest a new model of fruit maturation which initiates in internal tissues then radiates outwards.
- Yoshihito Shinozaki
- , Philippe Nicolas
- & Jocelyn K. C. Rose
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RNAs coordinate nuclear envelope assembly and DNA replication through ELYS recruitment to chromatin
The factors that link chromatin remodelling to nuclear envelope formation in the sperm pronucleus are not fully characterised. Here, the authors show that in RNA-depleted Xenopus laevis egg extracts, ELYS recruitment and nuclear pore complex formation are impaired, resulting in defective nuclear processes.
- Antoine Aze
- , Michalis Fragkos
- & Marcel Méchali
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RETRACTED ARTICLE: REST regulates the cell cycle for cardiac development and regeneration
The mechanisms regulating cardiomyocyte proliferation during development and cardiac regeneration are incompletely understood. The authors show that the transcription factor REST regulates cardiomyocyte proliferation by binding and repressing the cell cycle inhibitor p21.
- Donghong Zhang
- , Yidong Wang
- & Bin Zhou
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Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair
Zebrafish can regenerate damaged myocardial tissue but it is unclear how this is regulated. Here, the authors show that two TGF-β family members, Mstnb and Inhbaa, have opposite effects in regeneration, with mstnb overexpression or inhbaa loss-of-function causing cardiac scarring after injury.
- Deepika Dogra
- , Suchit Ahuja
- & Sven Reischauer
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miR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression
In the Drosophila testis, ageing leads to loss of germline stem cells. Here, the authors show that, during ageing in Drosophila, miR-9a is upregulated in male germline stem cells and regulates their proliferation by targeting N-cadherin.
- Yehonatan Epstein
- , Noam Perry
- & Hila Toledano
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Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis
The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones.
- Hjalte List Larsen
- , Laura Martín-Coll
- & Anne Grapin-Botton
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Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling
Cardiac trabeculae (which are sponge-like muscular structures) form mostly as a result of cardiomyocyte (CM) delamination in zebrafish. Here, the authors identify Nrg2a in zebrafish as a key regulator of trabeculation, and atrial and non-contractile CMs also respond to Nrg2a despite not forming trabeculae.
- S. Javad Rasouli
- & Didier Y. R. Stainier
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PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription
PTEN is a potent tumour suppressor involved in cell growth, proliferation and survival. Here the authors identify an N-terminal extended isoform of PTEN, termed PTENβ that negatively regulates ribosomal DNA transcription and cell proliferation, expanding the pleiotropic functions of the PTEN family.
- Hui Liang
- , Xi Chen
- & Yuxin Yin
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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.
- Thiviyani Maruthappu
- , Anissa Chikh
- & David P. Kelsell
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Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing
Androgen receptor is an important regulator of prostate development and cancer. In this study, the authors use genetic lineage tracing in mice to clarify the role of AR in different prostate epithelial cells.
- Qing Xie
- , Yueli Liu
- & Zhu A. Wang
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Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish
The adult zebrafish heart is capable of regeneration but the molecular mechanisms are poorly understood. Here the authors show that chromatin remodeling factor Brg1 represses cyclin-dependent kinase inhibitors to promote myocardial regeneration.
- Chenglu Xiao
- , Lu Gao
- & Jing-Wei Xiong
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Dephosphorylated parafibromin is a transcriptional coactivator of the Wnt/Hedgehog/Notch pathways
Normal epithelial intestine organisation requires Wnt and Hedgehog signalling activity. Here, the authors show that parafibromin can activate both pathways in a mutually exclusive manner and is important for intestinal homeostasis.
- Ippei Kikuchi
- , Atsushi Takahashi-Kanemitsu
- & Masanori Hatakeyama
Fused in sarcoma (FUS) inhibits milk production efficiency in mammals