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| Open AccessThree stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin
Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.
- Keitaro Fukuda
- , Yoshihiro Ito
- & Masayuki Amagai
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Article
| Open AccessJag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool
Dysregulation of basal progenitor cells induces esophageal tumorigenesis but the underlying mechanism is less explored. Here, the authors show that Jag1/2 deficiency promotes expansion of basal progenitor cells, leading to reduced squamous epithelial differentiation and enhanced formation of squamous cell carcinoma in the foregut.
- Haidi Huang
- , Yu Jiang
- & Yongchun Zhang
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Article
| Open AccessFused in sarcoma (FUS) inhibits milk production efficiency in mammals
Efficient milk production in mammals confers advantages by facilitating the transmission of energy from mother to offspring. However, the factors for establishing the efficiency in mammals are unknown. Here, the authors identify FUS as a regulator of efficient milk production in mammals.
- Haili Shao
- , Jipeng Huang
- & Baowei Jiao
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Article
| Open AccessAtypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions
The regulation of meiotic prophase progression varies between males and females. This study reveals the involvement of an atypical heat shock transcription factor HSF5 in gene expression during male meiotic prophase and highlights the involved gene regulatory mechanism.
- Saori Yoshimura
- , Ryuki Shimada
- & Kei-ichiro Ishiguro
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Article
| Open AccessNumb positively regulates Hedgehog signaling at the ciliary pocket
The precise regulatory mechanisms controlling ciliary Hedgehog signaling remain incomplete. Here, the authors use ciliary proteomics to reveal that Numb facilitates the endocytosis of the receptor Ptch1 from the ciliary pocket, thereby enabling activation of Hedgehog signaling.
- Xiaoliang Liu
- , Patricia T. Yam
- & Xuecai Ge
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Article
| Open AccessPhysiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation
Breastfeeding confers lifelong benefits to both mother and child, yet women worldwide experience lactation insufficiency. Here, the authors show that DNA damage occurring in the breast during pregnancy drives the generation of milk-producing cells.
- Rut Molinuevo
- , Julien Menendez
- & Lindsay Hinck
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Article
| Open AccessDifferentiation granules, a dynamic regulator of T. brucei development
The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
- Mathieu Cayla
- , Christos Spanos
- & Keith R. Matthews
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Article
| Open AccessEph-ephrin signaling couples endothelial cell sorting and arterial specification
Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.
- Jonas Stewen
- , Kai Kruse
- & Mara E. Pitulescu
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Article
| Open AccessA lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis
By tracing promoter expression in lineage-mapped single cells, Xu et al. present a whole-body cartography of microRNA transcriptional activities during C. elegans embryogenesis and demonstrate its broad utility in multifaceted functional analyses.
- Weina Xu
- , Jinyi Liu
- & Zhuo Du
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Article
| Open AccessTransient expression of the neuropeptide galanin modulates peripheral‑to‑central connectivity in the somatosensory thalamus during whisker development in mice
The function of transient neuropeptides in developmental roles in the nervous system remains elusive. Here, authors demonstrate that galanin shapes synaptic wiring in the whisker pathway, a fundamental sensory modality for infant rodents before eye opening.
- Zsofia Hevesi
- , Joanne Bakker
- & Tibor Harkany
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Article
| Open AccessHeterozygous missense variant in GLI2 impairs human endocrine pancreas development
Mutations in the Hedgehog signaling have not been previously associated to diabetes. Here, authors identify a missense variant of GLI2 in a family with early-onset diabetes and report an essential role of this gene during human iPSC-based pancreatic differentiation.
- Laura M. Mueller
- , Abigail Isaacson
- & Francesca M. Spagnoli
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Article
| Open AccessEvolutionary origin of Hoxc13-dependent skin appendages in amphibians
Hair is the main skin appendage of mammals. Here, the authors show that claws of clawed frogs and hair contain homologous keratins and depend on the same transcription factor, Hoxc13, suggesting a common evolutionary origin of these skin appendages.
- Marjolein Carron
- , Attila Placido Sachslehner
- & Leopold Eckhart
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Article
| Open AccessNotch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization
Sustained exogenous Notch2 signaling prompts Follicular B cells to trans-differentiate into Marginal Zone B cells. This study reveals that under physiological conditions, Notch2 signalling regulates a fate choice in antigen activated Follicular B cells, dictating whether they develop into Germinal Center B cells or Marginal Zone B cells.
- Tea Babushku
- , Markus Lechner
- & Lothar J. Strobl
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Article
| Open AccessM2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1
Adipose beiging is a positive biological change, which is often thought to be primarily sympathetically induced. Here, the authors show that M2 macrophages can independently promote beige adipogenesis, further revealing the adipocyte transcription factor Ets1 as a negative regulator of this process.
- Suyang Wu
- , Chen Qiu
- & Xiao Han
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Article
| Open AccessJAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development
The authors identified a cell population in Drosophila follicles that elaborate filopodia penetrating the oocyte they are contacting. These somatic cells are essential during oogenesis to regulate polarity and germline development of the future embryo.
- Charlotte Mallart
- , Sophie Netter
- & Marianne Malartre
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Article
| Open AccessTime-integrated BMP signaling determines fate in a stem cell model for early human development
The interpretation of the key developmental signal BMP remains poorly understood. Here, the authors show that the total time-integrated signaling controls differentiation in a stem cell embryo model and provide a possible mechanism.
- Seth Teague
- , Gillian Primavera
- & Idse Heemskerk
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Article
| Open AccessIn vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells
Early patterning of neural crest cells in the craniofacial primordium is important for its subsequent development. Here, authors establish in vitro model of branchial arch from human pluripotent stem cells for determining underlying mechanisms.
- Yusuke Seto
- , Ryoma Ogihara
- & Mototsugu Eiraku
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Article
| Open Access5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis
There is a strong need for the development of effective and safe disease-modifying osteoarthritis drugs. Here, the authors show that 5-ASA, an anti-inflammatory drug used for ulcerative colitis, shows promise in treating osteoarthritis in mice by improving cartilage and reducing inflammation even when administered at late stages of disease.
- Jihee Kim
- , Gina Ryu
- & Soo Young Lee
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Article
| Open AccessUbiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates
Upon cold exposure, two types of thermogenic fat cells, brown and beige adipocytes, are sequentially activated. Here, the authors show that E3 ubiquitin ligase RNF20 coordinates the sequential thermogenic activation through fat depot specific substrates.
- Yong Geun Jeon
- , Hahn Nahmgoong
- & Jae Bum Kim
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Article
| Open AccessSingle-cell multiomics decodes regulatory programs for mouse secondary palate development
Development of the secondary palate is a complex process. Here, the authors profile mouse palatogenesis through single-cell multiome sequencing, revealing dynamic gene regulation across embryonic days (E) 12.5, E13.5, E14.0, and E14.5.
- Fangfang Yan
- , Akiko Suzuki
- & Zhongming Zhao
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Article
| Open AccessCebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish
Eosinophils are innate immune cells critical for protection from parasites, but their developmental origin remains under studied. Here they analyze development of eosinophils in zebrafish and find that eosinophilic lineage commitment and differentiation are regulated by the Cebp1-Cebpβ axis.
- Gaofei Li
- , Yicong Sun
- & Yiyue Zhang
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Article
| Open AccessVGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification
Authors report that VGLL1 regulates cell fate determination and self-renewal of human pluripotent stem cell-derived trophectoderm-like cells and trophoblast stem cells via modulation of chromatin accessibility in cooperation with TEAD4.
- Yueli Yang
- , Wenqi Jia
- & Wenjuan Li
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Article
| Open AccessA full-body transcription factor expression atlas with completely resolved cell identities in C. elegans
Invariant cell lineage in C. elegans enables the analysis of transcriptional regulatory mechanisms controlling the fate of each cell at spatiotemporal resolution. Here, the authors develop a tool automating C. elegans cell identification and create an expression atlas of 620 transcription factors.
- Yongbin Li
- , Siyu Chen
- & Xiao Liu
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Article
| Open AccessCompartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage
The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory.
- David R. Ghasemi
- , Konstantin Okonechnikov
- & Kristian W. Pajtler
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Article
| Open AccessHistone lactylation couples cellular metabolism with developmental gene regulatory networks
While metabolic reprogramming has been shown to drive changes in cell identity, the link between cellular metabolism and gene expression remains poorly characterized. Here they show that histone lactylation couples metabolism and transcription during neural crest cell differentiation in the early embryo.
- Fjodor Merkuri
- , Megan Rothstein
- & Marcos Simoes-Costa
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Article
| Open AccessDeciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON
Deciphering the roles of gene regulation in cell fate decisions is crucial. Here, authors present CEFCON, a network-based framework that reveals cell-lineage-specific gene regulatory networks and identifies driver regulators controlling cell fate decisions from single-cell transcriptomics data.
- Peizhuo Wang
- , Xiao Wen
- & Jianyang Zeng
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Article
| Open AccessMyeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB
The mechanism underlying thyroid follicle formation is not well understood. Here, the authors show that a subgroup of NF-κB-activated thyrocytes, through interactions with myeloid cells, exhibit increased migration capacity to generate new follicles.
- Yang Rui-Meng
- , Song Shi-Yang
- & Song Huai-Dong
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Article
| Open AccessFate specification is spatially intermingled across planarian stem cells
Stem cells can select among a wide array of fates. Here, the authors utilize spatial transcriptomics and three-dimensional neighborhood analysis to uncover that fate choices in planarian stem cells occur in a highly intermingled pattern.
- Chanyoung Park
- , Kwadwo E. Owusu-Boaitey
- & Peter W. Reddien
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Article
| Open AccessEncystation stimuli sensing is mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
Giardia lamblia is an established model for studying encystation. Shih et al show bile and alkaline pH induce changes in membrane ordering, upregulate cAMP, and initiate encystation gene expression.
- Han-Wei Shih
- , Germain C. M. Alas
- & Alexander R. Paredez
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Article
| Open AccessA single cell genomics atlas of the Drosophila larval eye reveals distinct photoreceptor developmental timelines
The Drosophila eye is a powerful model system to study the dynamics of cell differentiation, cell state transitions, cell maturation, and pattern formation. Here, the authors report transcriptomic and chromatin accessibility data for all known cell types in the developing larval eye.
- Komal Kumar Bollepogu Raja
- , Kelvin Yeung
- & Graeme Mardon
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Article
| Open AccessFGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
Restoring salivary acinar cells after gland damage is a major clinical challenge. Here, authors identify FGF7-FGFR2-MAPK signaling as a regenerative target, critical for myoepithelial-acinar crosstalk that regulates seromucous acinar differentiation.
- Marit H. Aure
- , Jennifer M. Symonds
- & Matthew P. Hoffman
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Article
| Open AccessA branching model of lineage differentiation underpinning the neurogenic potential of enteric glia
The enteric nervous system encompasses the gut-intrinsic neuroglial networks that regulate gastrointestinal functions. Based on single-cell analysis, the authors propose a model in which neurogenic differentiation paths branch from a gliogenic trajectory.
- Anna Laddach
- , Song Hui Chng
- & Vassilis Pachnis
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Article
| Open AccessThe TNFR Wengen regulates the FGF pathway by an unconventional mechanism
Mechanistic studies of receptor action have aided our understanding of developmental processes and facilitated drug development. Here they show that the TNFR-Wengen acts by forming a complex with the FGFR-Breathless, regulating its activity during cell differentiation in the developing respiratory system of Drosophila.
- Annalisa Letizia
- , Maria Lluisa Espinàs
- & Marta Llimargas
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Article
| Open AccessMultimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis
Multimodal spatiotemporal transcriptomic resolution of palatal osteogenesis identifies previously unreported enriched genes in developing palate, paving the way toward viable diagnostic and therapeutic targets for cleft palate disorders.
- Jeremie Oliver Piña
- , Resmi Raju
- & Rena N. D’Souza
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Article
| Open AccessNotch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5
A subset of endocardial cells gives rise to hematopoietic cells which are important for the formation of cardiac valves. In this follow up study, authors report the molecular regulatory mechanisms behind the formation of macrophages in the heart.
- Norika Liu
- , Naofumi Kawahira
- & Atsushi Nakano
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Article
| Open AccessNvPrdm14d-expressing neural progenitor cells contribute to non-ectodermal neurogenesis in Nematostella vectensis
Endodermal neurogenesis is an uncommon trait among animals. Here they identify a population of endoderm-specific neural progenitor cells in the cnidarian Nematostella vectensis that is characterized by the expression of the transcription factor prdm14d.
- Quentin I. B. Lemaître
- , Natascha Bartsch
- & Fabian Rentzsch
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Article
| Open AccessTRIM28 modulates nuclear receptor signaling to regulate uterine function
This paper identifies Tripartite motif-containing 28 (TRIM28) as a novel modulator of steroid hormone signaling. TRIM28 deficiency disrupts uterine cell functions and composition leading to fertility defects
- Rong Li
- , Tianyuan Wang
- & Francesco J. DeMayo
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Article
| Open AccessA ubiquitin-based effector-to-inhibitor switch coordinates early brain, craniofacial, and skin development
The molecular mechanisms ensuring early face, brain, and skin formation are unclear. Here, the authors uncover a posttranslational pathway that controls cytoskeletal signaling circuits to coordinate ectodermal patterning and neurulation.
- Anthony J. Asmar
- , Shaun R. Abrams
- & Achim Werner
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Article
| Open AccessOpposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution
Researchers used single-nucleus RNA and ATAC sequencing to create an atlas of skeletal muscle development. They identified the gene programs and transcription factors that control muscle fiber development and maturation.
- Matthieu Dos Santos
- , Akansha M. Shah
- & Eric N. Olson
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Article
| Open AccessLactate-dependent transcriptional regulation controls mammalian eye morphogenesis
Using a combination of eye organoids and mouse models the authors identify a bioenergetic independent role of lactate as a cell signaling molecule required during early stages of eye formation in mice.
- Nozomu Takata
- , Jason M. Miska
- & Guillermo Oliver
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Article
| Open AccessTET2 and TET3 loss disrupts small intestine differentiation and homeostasis
DNA demethylation is known to be critical for the development and function of many tissues. Here the authors show that it is also required for intestinal lineage differentiation, and that mice lacking DNA demethylases have altered microbiomes and a predisposition to inflammation.
- Ihab Ansari
- , Llorenç Solé-Boldo
- & Yehudit Bergman
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Article
| Open AccessThe long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
The transcription factor ΔNp63 is a master regulator of epithelial development and integrity of stratified epithelial tissues. Here, the authors unveiled the lncRNA NEAT1 as an additional player of the highly complex regulatory network by which ΔNp63 controls epidermal homeostasis.
- Claudia Fierro
- , Veronica Gatti
- & Angelo Peschiaroli
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Article
| Open AccessIntracellular pH dynamics regulates intestinal stem cell lineage specification
Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu et al. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell.
- Yi Liu
- , Efren Reyes
- & Diane L. Barber
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Article
| Open AccessMaternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice
Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.
- Xue Jiang
- , Yu Cheng
- & Jianqiang Bao
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Article
| Open AccessDirected differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme
Mesenchymal lineages play critical roles during development, though these cells are frequently overlooked in directed differentiation models. Here they derive lung-specific mesenchyme from mouse iPSCs and generate organoids consisting of both mesenchymal and epithelial progenitors, observing functional epithelial-mesenchymal crosstalk.
- Andrea B. Alber
- , Hector A. Marquez
- & Darrell N. Kotton
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Article
| Open AccessSpatiotemporal transcriptomic atlas reveals the dynamic characteristics and key regulators of planarian regeneration
Cui et al. present a comprehensive three-dimensional spatiotemporal transcriptome landscape of planarian regeneration. They identified a novel pluripotent neoblast subtype and new spatially specific genes essential to tissue regeneration.
- Guanshen Cui
- , Kangning Dong
- & Yun-Gui Yang
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Article
| Open AccessUSP7 controls NGN3 stability and pancreatic endocrine lineage development
Tightly controlled NGN3 expression is essential for endocrine cell generation in the developing pancreas, with dysregulation leading to hyperglycemia in mice. Here they identify USP7 as a key post-translational regulator of NGN3 stability and show that this axis is required for endocrine development and beta-cell differentiation.
- Teodora Manea
- , Jessica Kristine Nelson
- & Rocio Sancho
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Article
| Open AccessEpigenetic landscape reveals MECOM as an endothelial lineage regulator
Errors in vascular development are associated with several congenital defects. Here they systematically investigated the epigenetic landscape of the endothelial lineage and found that MECOM depletion impairs endothelial cell differentiation and angiogenesis.
- Jie Lv
- , Shu Meng
- & Lili Zhang
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Article
| Open AccessA DBHS family member regulates male determination in the filariasis vector Armigeres subalbatus
The Armigeres subalbatus sex-determining locus, M, maps to the 3rd chromosome, but its identity was unknown. Here they identify a sex-specific gene, AsuMf, that is essential for male development and show that it is a novel male-determining factor derived from duplication and neofunctionalization of a conserved DBHS family member.
- Peiwen Liu
- , Wenqiang Yang
- & Xiao-Guang Chen