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Article
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Regulation of NSL by TAF4A is critical for genome stability and quiescence of muscle stem cells
Nuclear architecture depends on proper regulation of lamin A/C modifications. Here, the authors show that TAF4A and NF-Y control Kansl2 expression in muscle stem cells, preserving genome stability and supporting muscle regeneration.
- Angelina M. Georgieva
- , Krishna Sreenivasan
- & Thomas Braun
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| Open Access
Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
Here they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.
- Burak Ozkan
- , Mitzy Rios de Anda
- & Abdenour Soufi
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| Open Access
Pvf1-Pvr-mediated crosstalk between trachea and gut guides intestinal stem cell migration to promote gut regeneration
Adult stem cells often reside in specialized niches that they exit upon injury. Here they show that in Drosophila, after damage the gut-associated trachea produces the PDGF-VEGF-related ligand Pvf1, which acts as a guidance cue directing ISC migration toward injury sites.
- D. J. Mackay
- , A. John
- & D. S. Andersen
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| Open Access
Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection
Joint injury and disease are leading causes of disability, with mammalian joints exhibiting poor regenerative capacity. Here the authors showed that after loss of a whole joint, adult zebrafish regenerate de novo articular cartilage, ligament, and synovium into a complex joint organ.
- Maria Blumenkrantz
- , Felicia Woron
- & Joanna Smeeton
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| Open Access
Modular RNA interactions shape FXR1 condensates involved in mRNA localization and translation
Biomolecular condensates are dynamic compartments that regulate cellular functions. Here, the authors show that RNA motifs control the formation and localization of FXR1-containing condensates, linking riboregulation to nuclear pore function and fate transitions in human embryonic stem cells.
- Jiabin Yang
- , Zhongyang Chen
- & Jia Yu
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| Open Access
Contractile fibroblasts form a transient niche for the branching mammary epithelium
Fibroblasts represent a heterogenous cell population but how their differences reflect their plasticity and origin is not fully understood. Here, the authors map the origin and fate of a transient contractile fibroblast population that forms a niche supporting pubertal mammary gland branching and growth.
- Jakub Sumbal
- , Robin P. Journot
- & Silvia Fre
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| Open Access
Mechanical control of cell fate decisions in the skin epidermis
The mechanisms underlying cell fate decisions often remain unclear. Here, the authors develop a 3D vertex-based model of complex fate choices in skin epidermis and propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes.
- Preeti Sahu
- , Sara Monteiro-Ferreira
- & Edouard Hannezo
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| Open Access
Injectable therapeutic system incorporating neurogenesis-programmed stem cells concomitantly promoting muscle regeneration treats stress urinary incontinence
Stress urinary incontinence (SUI) is a significant clinical challenge where less invasive treatment strategies that also address the pathophysiology of SUI are desirable. Here, Fang et al. engineer an injectable, thermo-responsive composite hydrogel incorporated with programmed stem cells that provides structural support to the atrophic urethral sphincter and promotes urethral sphincter regeneration, angiogenesis, and neurogenesis as a treatment strategy for SUI.
- Wenzhuo Fang
- , Xuan Du
- & Ying Wang
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| Open Access
Concurrent temporal patterning of neural stem cells in the fly visual system
The temporal patterning of stem cells generates neural diversity in the nervous system. Here, the authors show that in the Drosophila optic lobe independent temporal mechanisms pattern the symmetric vs asymmetric stages of a neural stem cell lineage.
- Priscilla Valentino
- , Ishrat M. Islam
- & Ted Erclik
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BMAL1-TRIM28 represses transposable elements independently of CLOCK in pluripotent cells
Here, the authors find that BMAL1, best known for controlling the body clock, partners with TRIM28 in naïve pluripotent stem cells to repress retrotransposons.
- Amador Gallardo
- , Efres Belmonte-Reche
- & David Landeira
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| Open Access
Controlling nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity
Here, the authors develop pluripotent stem cell-derived kidney organoids by mimicking in vivo proximal differentiation, providing a model to study nephron development, injury responses, and a platform for therapeutic discovery.
- Jack Schnell
- , Zhen Miao
- & Nils O. Lindström
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Axial nephron fate switching demonstrates a plastic system tunable on demand
A versatile, human iPSC-derived nephron engineering platform that permits scrutiny of axial patterning mechanisms is critical for identifying the origins of human kidney disease. Here they describe a system in which synchronized human nephron structures are generated from pluripotent stem cells, enabling manipulation of axial segmentation.
- MaryAnne A. Achieng
- , Jack Schnell
- & Nils O. Lindström
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| Open Access
An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification
Thymic epithelial cells (TECs) are essential for T cell development but how they develop from progenitors in humans is difficult to study. Here authors set up an in vitro system for thymus organogenesis in which induced pluripotent stem cells give rise to mature and diverse TECs that fully support T cell differentiation.
- Yann Pretemer
- , Yuxian Gao
- & Yoko Hamazaki
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| Open Access
Modeling integration site data for safety assessment with MELISSA
Viral vector integration can affect the safety of gene and cell therapies. Here, authors introduce MELISSA, a regression-based statistical tool that quantifies integration site risks and clone growth effects, aiding the safety evaluation of therapies in both research and clinical settings.
- Tsai-Yu Lin
- , Giacomo Ceoldo
- & Danilo Pellin
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LncRNA HSCHARME is altered in human cardiomyopathies and promotes stem cell-derived cardiomyogenesis via splicing regulation
Cardiomyopathies are linked to dysregulated gene expression. Here, the authors identify the human long noncoding RNA HSCHARME as a disease-associated regulator of cardiomyocyte differentiation, acting through alternative splicing control.
- Giulia Buonaiuto
- , Fabio Desideri
- & Monica Ballarino
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| Open Access
Non-genetic neuromodulation with graphene optoelectronic actuators for disease models, stem cell maturation, and biohybrid robotics
Light can control neural activity but often requires genetic modification. Here, the authors present a graphene-based platform for non-genetic light controlled neuronal stimulation, enabling all-optical network analysis, stem cell derived neuron maturation, and closed-loop robotics.
- Elena Molokanova
- , Teng Zhou
- & Alex Savchenko
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| Open Access
Transposable element expression and sub-cellular dynamics during hPSC differentiation to endoderm, mesoderm, and ectoderm lineages
Transposable elements are genetic parasites that have colonised genomes and they express as parts of coding and noncoding RNAs. Here, the authors explore how they are expressed in transcripts in normal human development, and how they alter transcript dynamics.
- Isaac A. Babarinde
- , Xiuling Fu
- & Andrew P. Hutchins
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| Open Access
BMI1 regulates human erythroid self-renewal through both gene repression and gene activation
The limited proliferative capacity of erythroid precursors complicates the production of red blood cells for clinical purposes in vitro. Here, the authors show that erythroid proliferative capacity can be vastly increased by BMI1 overexpression, which regulates erythroid self-renewal through both gene repression and activation.
- Kathleen E. McGrath
- , Jayme L. Olsen
- & James Palis
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| Open Access
Basigin links altered skeletal stem cell lineage dynamics with glucocorticoid-induced bone loss and impaired angiogenesis
Glucocorticoid (GC) induced osteoporosis (GIOP) remains a significant clinical problem. Here, the authors find that GCs disrupt skeletal stem cell–endothelial crosstalk via Basigin that can be targeted as a potential therapy for GIOP.
- Thomas H. Ambrosi
- , David Morales
- & Nancy E. Lane
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| Open Access
Snhg18 regulates Yap subcellular localization to maintain bone homeostasis
Huang et al. identify that lnc-Snhg18 promotes BMSCs osteogenesis by facilitating Cav1–Ywhah interaction and Yap nuclear translocation. Loss of Snhg18 worsens bone loss, while delivery restores bone mass, suggesting a therapeutic target for osteoporosis.
- Jie Huang
- , Yuteng Weng
- & Zuolin Wang
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| Open Access
REST/NRSF Preserves muscle stem cell identity by repressing alternate cell fate
Here the authors show that REST/NRSF represses non-muscle lineage genes in muscle stem cells and progenitors, preserving their identity and differentiation capacity. Loss of REST disrupts gene silencing, impairs muscle regeneration, and leads to stem cell pool depletion.
- Korin Sahinyan
- , Darren M. Blackburn
- & Vahab D. Soleimani
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| Open Access
Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells
Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.
- Sayandeep Saha
- , W. John Haynes
- & Matthew E. Brown
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| Open Access
Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential
This study presents an experimental system to conditionally immortalize murine megakaryocyte-erythroid progenitor cells, providing a versatile system for investigation of red blood cell and platelet biology in vitro and in vivo.
- Ruiqiong Wu
- , Faraz Salehi
- & Hans Häcker
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| Open Access
Cross-species comparison reveals therapeutic vulnerabilities halting glioblastoma progression
Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.
- Leo Carl Foerster
- , Oguzhan Kaya
- & Ana Martin-Villalba
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| Open Access
Aging affects reprogramming of pulmonary capillary endothelial cells after lung injury in male mice
Here the authors report single-cell and spatial transcriptomics of young and aged male fibrotic mouse lungs. Age-related alterations in capillary sub-populations are associated with a proangiogenic phenotype linked to regeneration of the alveolar niche.
- Marin Truchi
- , Marine Gautier-Isola
- & Bernard Mari
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| Open Access
USP17L promotes the 2-cell-like program through deubiquitination of H2AK119ub1 and ZSCAN4
USP17L, encoded by a gene family expressed in mouse 2-cell embryos and 2-cell-like cells, is shown to promote the 2-cell program in mESCs at both transcriptional and post-translational levels, in part through deubiquitinating H2AK119ub1 and ZSCAN4.
- Panpan Shi
- , Xukun Lu
- & Lin Liu
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Article
| Open Access
METTL9 sustains vertebrate neural development primarily via non-catalytic functions
Here the authors show thatMETTL9 enzyme sustains neural development in vertebrates by maintaining the secretory pathway, mainly independently of METTL9 catalytic activity. METTL9 loss in cells leads to Golgi fragmentation.
- Azzurra Codino
- , Luca Spagnoletti
- & Luca Pandolfini
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| Open Access
DynaTag for efficient mapping of transcription factors in low-input samples and at single-cell resolution
Transcription factors shape cell identity, but mapping their genomic targets remains challenging. Here the authors present DynaTag, a modified CUT&Tag method for profiling TF occupancy in bulk and single cells, and apply it to assess changes in TF activity in SCLC tumours following chemotherapy.
- Pascal Hunold
- , Giulia Pizzolato
- & Robert Hänsel-Hertsch
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| Open Access
Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst
The authors show human embryo lineage specification in the blastocyst is driven by differential FGF/ERK signaling, which segregates yolk sac-fated hypoblast and embryonic epiblast. They establish naïve embryonic stem cells based on these insights.
- Claire S. Simon
- , Afshan McCarthy
- & Kathy K. Niakan
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| Open Access
The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth
The skin has a remarkable ability to grow under stretch, though the underlying mechanisms remain unclear. Here, the authors show that the mechanosensor Piezo1 coordinates metabolic and immune responses to drive tension-induced skin growth.
- Yingchao Xue
- , Elizabeth Winnicki
- & Luis A. Garza
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| Open Access
The histone H3 lysine 36 demethylase KDM2A/FBXL11 controls Polycomb-mediated gene repression and germ cell development in male mice
Here, the authors show that KDM2A regulates cell cycle progression, modulation of H3K36me2 and H3K27me3 chromatin states and gene repression which are critical for survival of differentiating spermatogonia. KDM2A regulates progression through meiosis as well.
- Michael T. Bocker
- , Grigorios Fanourgakis
- & Thomas B. Nicholson
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| Open Access
Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis
Single-cell multi-omics in Drosophila testis reveals enhancer-driven gene regulatory networks and shows how Wnt signaling and key transcription factors orchestrate stem cell maintenance and lineage progression during early spermatogenesis.
- Patrick van Nierop y Sanchez
- , Pallavi Santhi Sekhar
- & Ingrid Lohmann
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Article
| Open Access
Age mosaic of gut epithelial cells prevents aging
Qin et al. suggest how organ or individual aging can be understood at the level of cellular age composition. An age mosaic among Drosophila gut epithelial cells prevents aging, suggesting that a tissue age mosaic may inform therapeutics to reverse aging.
- Peizhong Qin
- , Qi Wang
- & Zheng Guo
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Article
| Open Access
Intestinal tuft cell subtypes represent successive stages of maturation driven by crypt-villus signaling gradients
Intestinal tuft cell subtypes represent successive stages of differentiation that is driven by crypt-villus signaling gradients. Here, the authors show that applying these gradients to organoids generates mature immune-related chemosensory tuft cells suitable for experimental studies.
- Julian R. Buissant des Amorie
- , Max A. Betjes
- & Hugo J. G. Snippert
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| Open Access
Stem cell secretome armed magneto-actuated micromotors as spatio-temporal manipulators for wound healing acceleration
Deep wound healing faces challenges due to poor drug penetration and uncoordinated repair processes. Here, the authors show that stem cell secretome micromotors actively penetrate wounds, accelerating healing by enhancing tissue regeneration and reducing inflammation across species.
- Jiamiao Jiang
- , Haiying Liang
- & Yingfeng Tu
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| Open Access
Basement membrane perforations guide anterior–posterior axis formation
Chen et al. show that in mice, extracellular matrix remodeling drives early migration of the anterior signaling center, establishing the body axis sooner than expected—a mechanism potentially conserved in humans.
- Dong-Yuan Chen
- , Nikolas H. Claussen
- & Magdalena Zernicka-Goetz
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| Open Access
Quantitative phase imaging with temporal kinetics predicts hematopoietic stem cell diversity
This study introduces a label-free imaging and machine learning platform that predicts hematopoietic stem cell function based on their dynamic behaviors, offering new insights into stem cell diversity and potential clinical applications.
- Takao Yogo
- , Yuichiro Iwamoto
- & Satoshi Yamazaki
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Article
| Open Access
Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes
Proliferation of adult tissue stem cells is tightly regulated to balance maintenance of the tissue against stem cell exhaustion or cancerous expansion. Here they show that zebrafish lateral line progenitors are differentially regulated by two cyclinD genes, which control developmental and adult progenitor proliferation as well as hair cell polarization.
- Mark E. Lush
- , Ya-Yin Tsai
- & Tatjana Piotrowski
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| Open Access
Phase separated condensates of ATRX regulate neural progenitor identity
Tomooka et al. demonstrate that phase-separated ATRX condensates play an essential role in maintaining human neural progenitor identity through chromatin regulation and transcriptional control.
- Ryo Tomooka
- , Tsukasa Sanosaka
- & Jun Kohyama
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Article
| Open Access
Microtopography-induced changes in cell nucleus morphology enhance bone regeneration by modulating the cellular secretome
Nuclear morphology plays a critical role in regulating gene expression and cell function. Here, Wang et al. report that topography-induced nuclear deformation enhances the secretome of hMSCs, promoting extracellular matrix (ECM) organization and facilitating bone regeneration through matricrine effects.
- Xinlong Wang
- , Yiming Li
- & Guillermo A. Ameer
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Article
| Open Access
Combining phenomics with transcriptomics reveals cell-type-specific morphological and molecular signatures of the 22q11.2 deletion
Here, authors use NeuroPainting, a high-content imaging assay, to reveal cell-type-specific effects of 22q11.2 deletion in neural cells, linking adhesion gene dysregulation to mitochondrial and structural abnormalities, especially in astrocytes.
- Matthew Tegtmeyer
- , Dhara Liyanage
- & Ralda Nehme
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Article
| Open Access
EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress
A new study shows EMP1 protects hematopoietic stem cells by suppressing sphingolipid metabolism and ER stress. EMP1 interacts with CERS2 to limit dihydroceramide production, which causes protein aggregation when elevated.
- Lei Li
- , Yufei Lei
- & Yu Hou
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Article
| Open Access
Nuclear morphometrics coupled with machine learning identifies dynamic states of senescence across age
Aging leads to progressive loss of effective tissue regeneration, which has been linked to the accumulation of senescent cells. Here, the authors use machine learning to identify a stable nuclear morphometric phenotype that detects senescent cells across tissues and age, enabling their quantification and mapping in diverse environments.
- Sahil A. Mapkar
- , Sarah A. Bliss
- & Michael N. Wosczyna
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Article
| Open Access
Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses
Stem cells are highly resistant to viral infection, irrespective of any interferon response. Here the authors discover that VAMP5 as a potent cell-autonomous defense factor protects ESCs from various viruses’ infection, including SARS-CoV-2 by interacting with RNA replication complexes to defend against viral infection.
- Huijun Dong
- , Zihang Pan
- & Kuanhui Xiang
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Article
| Open Access
Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia
This study leverages single-nucleus multiomics to map cellular senescence atlas in aging human skeletal muscle and uncovers potential targets and senotherapeutics for treating age-associated sarcopenia.
- Yang Li
- , Chuhan Li
- & Huating Wang
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Article
| Open Access
Pancreatic β-cell regeneration in situ by the ALK3 agonist THR-123
Álvarez-Cubela et al. show that a BMP-7-like peptide induces β-cell regeneration and lowers hyperglycemia in diabetic mice, and reveal the transition of ductal cells into insulin-expressing cells. These results have potential therapeutic implications
- Silvia Álvarez-Cubela
- , Isabella D. Altilio
- & Juan Domínguez-Bendala
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Article
| Open Access
Lipoic acid functions in Paneth cells to prevent human intestinal stem cell aging
This study reveals that α-lipoic acid (ALA) is reduced in aged mouse and human intestine and ALA supplementation reduces aging hallmarks. Paneth cells play a role in the effects of ALA.
- Zehong Zhang
- , Qianyi Wan
- & Haiyang Chen
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Article
| Open Access
Decreased non-neurogenic acetylcholine in bone marrow triggers age-related defective stem/progenitor cell homing
The ability of bone marrow to recruit transplanted hematopoietic stem cells decreases with age. Here, the authors demonstrate that this decline is caused by reduced sinusoidal shear stress due to increased non-neuronal acetylcholine degradation.
- Takayuki Morikawa
- , Shinya Fujita
- & Keiyo Takubo
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Article
| Open Access
Single-cell transcriptomics reveals BMP4-BMPR2 signaling promotes radiation resistance in hematopoietic stem cells following injury
The heterogeneity of HSPCs in response to IR stress remains poorly characterized. Here, the authors provide insights into the molecular intricacies of IR-induced BM injury and reveal the roles of BMP4-BMPR2 signaling in radiation resistance of HSCs.
- Yanhua Li
- , Yunxing Li
- & Gangqiao Zhou
Stage-specific and cell-autonomous functions of Delta-like 1 in skeletal muscle stem cells and myogenesisBrowse broader subjects
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