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| Open AccessAn in vivo and in vitro spatiotemporal profile of human midbrain development
This study provides a comprehensive profile of human fetal midbrain development and its comparison with lab-grown midbrain cultures. These findings demonstrate that midbrain organoids recapitulate fetal developmental stages while capturing essential spatial and molecular characteristics, relevant to dopamine-related disorders.
- Dimitri Budinger
- , Pau Puigdevall
- & Serena Barral
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Article
| Open AccessMosaic partial epidermal reprogramming remodels neighbors and niches to refine skin homeostasis and repair
Here, the authors show that transient, mosaic induction of Yamanaka factors in the epidermis can promote skin repair beyond reprogramming cells. They also influence neighboring epithelial cells and immune–mesenchymal niches by reshaping injury response programs.
- Minjun Kwak
- , Eunjun Choi
- & Sekyu Choi
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Article
| Open AccessMechanically heterogeneous hydrogel with cell-programmed network restructuring promotes tissue regeneration by mechano-epigenetic modulation
The mechanical microenvironment for MSCs is crucial for osteogenesis. Here, the authors developed a hydrogel in which MSC-secreted ALP actively remodels the surrounding heterogeneous mechanical microenvironment to promote osteogenesis for bone regeneration.
- Qiangjun Ling
- , Hao Li
- & Liming Bian
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Article
| Open AccessImpaired stem cell migration and divisions in Duchenne muscular dystrophy revealed by live imaging
Using live-imaging in vivo and ex vivo, Sarde et al. show that dystrophic muscle stem cells have precocious differentiation through symmetric divisions and impaired migration, with differential impact of the myofibre niche upon cross-transplantation.
- Liza Sarde
- , Gaëlle Letort
- & Brendan Evano
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Article
| Open AccessThe Drosophila proventriculus lacks stem cells but compensates for age-related cell loss via endoreplication-mediated cell growth
This study demonstrates that the Drosophila proventriculus, the structure at the anterior of gut that synthesizes the peritrophic membrane, lacks stem cells but undergoes continual endocycling to compensate for cells loss during aging or damage.
- Ben Ewen-Campen
- , Weihang Chen
- & Norbert Perrimon
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Article
| Open AccessThe functional landscape of alternative splicing in hematopoietic lineage commitment
Alternative splicing greatly expands the transcriptomic and proteomic diversity in vertebrates. Here, the authors develop a machine-learning tool to identify functional splicing events during hematopoietic cell differentiation, revealing new regulators of hematopoiesis.
- Xiao Hu
- , Jinrui Wang
- & Lu Chen
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Article
| Open AccessOlig2 acts as an inducible barrier to in vivo astrocyte-to-neuron conversion
Astrocyte-to-neuron (AtN) conversion is limited by intrinsic barriers, hindering its efficiency. Here, the authors show that Olig2 acts as an inducible barrier to in vivo Ngn2-mediated AtN conversion, reducing reprogramming efficiency.
- Chuying Lai
- , Kaiyu Hou
- & Zheng Wu
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Article
| Open AccessModulation of Nudt21 levels reveals dose-dependent roles of alternative polyadenylation in tissue regeneration
Nudt21-mediated 3′UTR regulation orchestrates tissue regeneration through dose-dependent control of stem cell differentiation and multiprotein complex assembly, revealing alternative polyadenylation as essential for organismal survival.
- Nikolaos Tsopoulidis
- , Masaki Yagi
- & Konrad Hochedlinger
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Article
| Open AccessIn vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis
A CRISPR screen reveals that loss of structural components of the SAGA complex derails hematopoiesis by decoupling epigenetic control. This halts stem cell maturation, triggers a pathogenic interferon program and boosts human MDS-L cell growth.
- Archana Shankar
- , Leonid Olender
- & Adam C. Wilkinson
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Article
| Open AccessStress vesicles link epidermal mechanotransduction to stem cell differentiation
Using two-photon intravital imaging, the authors show that mechanical stress in skin triggers fluid-filled “stress vesicles” in epidermal cells, altering Piezo1-dependent calcium signals to drive stem cell differentiation and protect tissue integrity.
- Sixia Huang
- , Paola Kuri
- & Panteleimon Rompolas
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Article
| Open AccessRoboA reinforces planarian stem cell fate through FoxA and Anosmin1a
Pluripotent stem cells are found throughout the planarian body but regenerate organs in distinct regions. This study shows that the receptor RoboA and the secreted protein Anosmin1a act as signals that restrict stem cell plasticity and differentiation.
- Kuang-Tse Wang
- , Fu-Yu Tsai
- & Carolyn E. Adler
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Article
| Open Access
Endothelial stem cells of the retinal vasculature reside in the optic nerve
This study finds stem-like endothelial cells in the optic nerve that supply and repair retinal blood vessels after injury, revealing a hierarchical repair system that may enable new treatments for blinding vascular eye diseases.
- Susumu Sakimoto
- , Toru Takigawa
- & Kohji Nishida
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Article
| Open AccessCombinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development
In vitro methods for thymic organoid cultures are useful to examine requirements for T cell development and for generating large numbers of cells for therapeutic purposes. Here the authors use human induced pluripotent stem cells, differentiate these into thymic epithelial organoid cultures and utilise haematopoietic progenitors to show development of T cells in vitro.
- Nathan Provin
- , Manon d’Arco
- & Matthieu Giraud
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Article
| Open AccessComparative multi-omic analysis reveals conserved and derived mechanisms of fin and limb regeneration
Here they compare fin and limb regeneration at the single-cell and genomic level, revealing conserved mechanisms and unique adaptations that shaped the evolution of vertebrate appendage regeneration.
- Josane F. Sousa
- , Gabriela Lima
- & Igor Schneider
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Article
| Open Access
Antibody-conjugated mesenchymal stromal cell drug delivery system for the treatment of autoimmune diseases in mice
Antibody-conjugated Mesenchymal stromal cells (Ac-MSC) carrying internalized therapeutic agents represent a promising therapeutic approach for the treatment of autoimmune disease. Here, an ac-MSC-based drug delivery system, consisting of anti-CD4 antibody-conjugated MSCs loaded with a RORγt inverse agonist, is engineered to achieve selective targeting of pathogenic CD4 T cells and to deliver therapeutic benefits in mouse models of psoriasis and arthritis.
- Qian Xie
- , Yanni Shen
- & Yan Wang
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Article
| Open AccessPURE-seq integrates FACS and PIP-seq for single-cell genomics of ultra-rare cells
Rare cells are often biologically and clinically important, but their low abundance makes them challenging to study using single-cell transcriptomics. Here, the authors develop PURE-seq which integrates FACS and PIP-seq to directly sequence ultra-rare cells. It captures cells at 1 in 1,000,000 rarity, which the authors demonstrate by profiling circulating tumor cells and identifying Egr1 as a regulator of mouse hematopoietic stem cell aging.
- Sixuan Pan
- , Inés Fernández-Maestre
- & Adam R. Abate
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Article
| Open AccessDivergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells
This study investigates the impact of parity on aging in the mammary gland. The authors find that aging leads to the accumulation of abnormal IL33+ hybrid epithelial cells in nulliparous mice, whereas parity significantly restricts this population.
- Andrew Olander
- , Paloma Medina
- & Shaheen S. Sikandar
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Article
| Open AccessWDR5 remodels NANOG condensates to drive transcriptional programs and sustain stem cell identity
This study shows that WDR5 remodels NANOG condensates to control transcriptional programs. Disrupting their interaction compromises stem cell identity and suppresses leukemia stem cell expansion.
- Duo Wang
- , Xianle Shi
- & Yanjing Li
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Article
| Open AccessDNA methylation and lncRNA control asynchronous DNA replication at specific imprinted gene domains
It is not fully understood why genomic loci show asynchronous DNA replication. Here, the authors show that two imprinted gene domains replicate asynchronously between the parental chromosomes due to differential DNA methylation and non-coding RNA, leading to allelic differences.
- Yui Imaizumi
- , François Charon
- & Robert Feil
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Article
| Open AccessEpendymoglial cells are critical for cortex regeneration in axolotls
Here they establish an NTR-based genetic ablation tool in axolotls to investigate the function of specific cells. They use this system to demonstrate the capacity of ependymoglial cells for central nervous system regeneration.
- Sulei Fu
- , Yan-Yun Zeng
- & Ji-Feng Fei
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Article
| Open AccessOTX2 inhibits human pluripotent stem cell reprogramming toward 8-cell-like and morula-like states
OTX2 acts as a barrier to the formation of human 8-cell-like and morula-like cells in vitro. Deleting OTX2 enhances their induction efficiency and developmental potential, uncovering key mechanisms of totipotency regulation and early human development.
- Xi Kong
- , Nan Jiang
- & Bingqing Xie
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Article
| Open AccessG9a-mediated H3K9me2 orchestrates intestinal epithelial regeneration through epigenetic silencing of cell cycle-related genes
Here they show that G9a-mediated H3K9me2 regulates intestinal homeostasis and injury repair through repression of cell cycle arrest genes in both mouse and human.
- Jingzhou Chen
- , Xiaoliang Shi
- & Jinghao Sheng
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Article
| Open Access
A scalable two-step genome editing strategy for generating full-length gene-humanized mice at diverse genomic loci
Humanized mice bearing full-length human genes recapitulate human biology but are challenging to generate. Here, the authors develop TECHNO, a twostep CRISPR–ES cell method that efficiently replaces mouse loci with >200-kbp human orthologs, enabling versatile in vivo disease modeling.
- Jumpei Taguchi
- , Mio Kikuchi
- & Manabu Ozawa
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Article
| Open AccessTranscriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice
The function of intermediate epithelial states in pulmonary fibrosis unknown. This study used RNA sensing technology to show selectively removal of alveolar epithelial stem cells trapping in an intermediate state reduced lung fibrosis.
- Fei Peng
- , Chun-sun Jiang
- & Yong Zhou
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Article
| Open AccessVolumetric compression regulates the phase separation of AXIN and acts as an operational amplifier to bidirectionally modulate Wnt signaling in organoids
The scaffold protein AXIN can promote the formation of two opposing complexes: the Wnt signalosome and a degradation complex that inhibits Wnt. Here, the authors show that mechanical compression and the presence/absence of Wnt ligand are inputs in a circuit that acts as a logic gate to control which complex is formed.
- Jinyun Shi
- , Linze Wu
- & Yiwei Li
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Article
| Open Access
The dorsal aortic compartment is a developmental source of brown adipose tissue in mice
The somitic mesoderm is seen as the main source of brown adipose tissue, although some depots are of partially unknown origin. Here, the authors show that Osr1 labels multipotent dorsal aorta progenitors at E9.5 that contribute to cartilage, muscle, and adipose tissues, revealing a non-somitic contribution to several brown adipose depots.
- Sophie Heider
- , Cornelius Fischer
- & Sigmar Stricker
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Article
| Open AccessOxidative stress and GPX2 control pancreatic vs. non-pancreatic cell fate in human endoderm
The role of metabolic processes in endoderm differentiation remains elusive. Here, the authors discover that oxidative stress and GPX2 determine whether human stem cells differentiate into pancreatic or liver tissue. This finding could improve cell-based therapies for diabetes and liver diseases.
- Joanna Szpotkowska
- , Wojciech J. Szlachcic
- & Malgorzata Borowiak
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Article
| Open Access
Autologous cell therapy with CD133+ bone marrow-derived stem cells for Asherman Syndrome: a phase 1/2 trial
The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.
- Xavier Santamaria
- , María Pardo-Figuerez
- & Carlos Simon
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Article
| Open Access
Rapid endothelialization of printed vascular grafts by perivascular niche-circulating endothelial progenitors crosstalk
Fast reendothelialisation of vascular grafts is important for maintain patency. Here, the authors report on a vascular graft that regenerates the neo-adventitia with lymphatic endothelial cells, which increases the recruitment of circulatory progenitor cells, achieving 90% patency in small-diameter arterial grafts.
- Zhe-qian Zhang
- , Ping-Ping Yuan
- & Wei Wu
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Article
| Open Access
IL-17a induces age-related olfactory dysfunction by impairing regeneration and promoting respiratory metaplasia in mice
The olfactory epithelium (OE) undergoes changes during aging and this may affect inflammatory responses and immune cell infiltration. Here the authors look at the effect of aging on OE and how this involves cross talk between T cells and horizontal basal cells involving Il17a expression in OE which is increased in aging and inhibition of IL-17a function reduces respiratory metaplasia.
- Shenglei Wang
- , Xudong Cha
- & Wenwen Ren
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Article
| Open Access
FGF7 promotes load-bearing tendon regeneration and suppresses fibrosis
Growth factor signalling has been shown to alleviate tissue fibrosis and promote repair. Here, the authors use fibroblast growth factor 7 (FGF7) knockout mice and an FGF7-loaded hydrogel to show that this factor can promote functional regeneration of tendon.
- Ruifu Lin
- , Junchao Luo
- & Zi Yin
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Article
| Open Access
Lymphatic–stem cell crosstalk promotes tendon regeneration via Notch1–Srebp2–mediated cholesterol metabolism
Tendons exhibit limited healing capacity and the role of lymphatic vessels in tendon regeneration is largely overlooked. Here they compare control and injured tendon cells from both neonatal and adult mice and identify lymphatic vessels as key regenerative niche elements.
- Liujing Chen
- , Meilian Cai
- & Ruili Yang
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Article
| Open Access
Restoration of PKM1 improves functional maturation of human stem-cell derived-β cell by regulating PEP metabolism
Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation of stem cell–derived islets for diabetes therapy.
- Haopeng Lin
- , Xin Liu
- & Huisheng Liu
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Article
| Open Access
H2AK119ub dynamics control hair follicle stem cell quiescence
This study uncovers H2AK119ub as a conserved dynamic molecular switch that maintains stem cell quiescence and regenerative potential, revealing how chromatin dynamics regulate stem cell states across species.
- Pooja Flora
- , Meng Yen Li
- & Elena Ezhkova
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Article
| Open Access
Local therapeutic platform prevents postsurgical GBM recurrence by diminishing GICs and reshaping immunosuppressive microenvironment
Glioblastoma multiforme (GBM) recurrence driven by residual glioma-initiating cells (GICs) and immunosuppressive microenvironment presents a significant clinical challenge. Here, they report an injectable therapeutic platform that targets remaining GICs and reverses the immunosuppressive microenvironment after postoperative resection to prevent the recurrence of GBM.
- Mengxi Zhu
- , Mengting Yang
- & Huining He
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Article
| Open Access
S100B triggers neuroendocrine macrophage networks to drive airway regeneration in mice
This study identifies S100B as a regulator of communication between pulmonary neuroendocrine cells and macrophages during airway repair, revealing an S100B-arginase-1 pathway that may be leveraged to enhance lung regeneration.
- Bing Sun
- , Haiting Dai
- & Yiming Xing
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Article
| Open Access
METTL3 safeguards cell identity and epigenome of human trophoblast stem cells
METTL3 promotes healthy placenta function by regulating m6A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.
- Haifeng Fu
- , Chunxiao Chen
- & Pentao Liu
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Article
| Open Access
TRIM37–PARP1–TET1 axis maintains stemness and prevents osteoporosis by inhibiting DNMT1 alternative splicing via 5hmC regulation
TRIM37–PARP1–TET1 signalling preserves stem cell function and prevents osteoporosis by regulating DNMT1 splicing through 5hmC maintenance, revealing a mechanism linking epigenetic control to stem cell function and bone health.
- Chun-Te Ho
- , Ling-Hui Li
- & Shih-Chieh Hung
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Article
| Open Access
Whole body regeneration deploys a rewired embryonic gene regulatory network logic
To what extent regeneration recapitulates embryonic development is a longstanding question. Here, they show that embryonic gene modules are re-used, rewired, and interconnected to specific injury-induced down-stream targets during regeneration.
- Rita Andreoni-Pham
- , Hereroa Johnston
- & Eric Röttinger
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Article
| Open Access
C1q drives neural stem cell quiescence by regulating cell cycle and metabolism through BAI1
The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.
- Katja M. Piltti
- , Anita Lakatos
- & Aileen J. Anderson
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Article
| Open Access
Nociceptive sensory neuron-derived NGF orchestrates a fibrotic mesenchymal stromal cell neurogenic niche to drive tendon pathological fibrosis
Nociceptive sensory nerves infiltrate the peripheral trauma area, mediating the biased repair response due to the formation of fibrotic mesenchymal stromal cells (MSCs) neurogenic niche. Nociceptive sensory neuron-derived nerve growth factor activates the TrkA receptors in MSCs and triggers the Hif1α-Twist1 pathway, driving the differentiation of MSCs into myofibroblasts to mediate fibrosis. TPX-0005 exerts therapeutic effects by inhibiting TrkA to reverse fibrosis.
- Yanhao Li
- , Sa Pang
- & Shen Liu
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Article
| Open Access
Wnt signaling restores evolutionary loss of robust foot regeneration rates in Hydra
Regeneration varies dramatically even between closely related species. Here they show that the evolutionary loss of foot regeneration observed in Hydra oligactis stems from weak Wnt activation after injury. Transient Wnt activation restores foot regeneration and the expression of foot transcription factor dlx2.
- Sergio E. Campos
- , Sahar Naziri
- & Celina E. Juliano
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Article
| Open Access
Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models
Sinus node dysfunction (SND) is a prevalent arrhythmia syndrome characterized by sinoatrial node pacemaker failure. This study engineers stem cell-derived vesicles with platelet membranes for targeted delivery to the ischemic sinoatrial node as a cell-free nanotherapeutic strategy for treatment of SND.
- Hanfeng Liu
- , Yangxi Zeng
- & Bin Liao
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Article
| Open Access
Chemical reprogramming of fibroblasts into retinal pigment epithelium cells for vision restoration
This study presents a two-step chemical reprogramming strategy that converts fibroblasts into functional retinal pigment epithelium cells, offering a safe and scalable alternative for vision restoration in retinal degenerative diseases.
- Shasha Li
- , Hui Liu
- & Jianzhong Su
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Article
| Open Access
Monitoring rapid degradation of NANOG reveals UTP15 maintains pluripotency by regulating nascent transcripts
This study shows that the transcriptional targets of NANOG recruits UTP15 to gene promoters in mESCs. There, UTP15 supports the formation of Pol II condensates, thereby activating pluripotency gene transcription independently of its classic role.
- Mingqiang Deng
- , Dongmei He
- & Xichen Bao
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Perspective
| Open Access
Reversibility, regulation, and the community of development: the legacy of Sir John B. Gurdon
- Richard P. Halley-Stott
- , Eva Hörmanseder
- & Vincent Pasque
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Article
| Open Access
Elimination of a neutrophil Pad4 byproduct restores stem cell–mediated bone regeneration in hyperglycemia
Here they show that high blood sugar drives neutrophils to release 4-GBA, a Pad4 byproduct that blocks bone-forming stem cells. A peptide gel that traps 4-GBA restores jawbone healing in rats, rabbits and dogs, suggesting a local, immune-sparing therapy.
- Liqiang Zhang
- , Jia Li
- & Wenjia Liu
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Article
| Open Access
A niche-dependent redox rheostat regulates epithelial stem cell fate
Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.
- Xi Chen
- , Krishnan Raghunathan
- & Jay R. Thiagarajah
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Article
| Open Access
Chromatin accessibility in stem cells unveils progressive transcriptional alterations in myelodysplastic syndrome
This study reveals that MDS stem cells progressively acquire progenitor-like chromatin features during disease progression, and that a scoring system based on chromatin accessibility in MDS stem and progenitor cells correlates strongly with disease progression.
- Motohiko Oshima
- , Naoya Takayama
- & Atsushi Iwama
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