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| Open AccessNuclear actin structure regulates chromatin accessibility
Intranuclear actin contributes to nuclear structure. Inducing actin remodeling within the nucleus regulates chromatin accessibility, and is associated with phenotypic outcomes in mesenchymal stem cells. As such, dynamic actin remodeling may modulate gene expression.
- Buer Sen
- , Zhihui Xie
- & Janet Rubin
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Article
| Open AccessTargeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow
Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1.
- Tongling Huang
- , Zhaocheng Lu
- & Min Guan
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Article
| Open AccessSOXC are critical regulators of adult bone mass
Angelozzi et al. uncover key mechanisms involved in physiological and pathological bone mass remodeling by showing that SOXC transcription factors regulate the bone formation and resorption balance via critical roles in LepR+ mesenchymal stem cells.
- Marco Angelozzi
- , Anirudha Karvande
- & Véronique Lefebvre
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| Open AccessStem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice
The role of stem Leydig cells in restoration of male fertility after acute injury is not clear. In an acute injury mouse model of testicular torsion, the authors show that Stem Leydig cells can restore testicular immunological homeostasis by mitochondria transfer to macrophages in a TRPM7-mediated manner.
- Ani Chi
- , Bicheng Yang
- & Min Zhang
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| Open AccessReassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models
Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.
- Jia Cao
- , Ling Jin
- & Hui Xie
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Article
| Open AccessDPPIV+ fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages
Although macrophages infiltrating the skeletal muscles are known to be important in muscle growth and repair, much less is known about muscle-resident macrophages. Here, the authors identify a fibro-adipogenic progenitor niche involved in the maintenance of skeletal muscle-resident macrophages.
- Farshad Babaeijandaghi
- , Nasim Kajabadi
- & Fabio M. V. Rossi
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Article
| Open AccessAcoustofluidic Interfaces for the Mechanobiological Secretome of MSCs
Efficient production of MSC secretome for therapeutic applications remains a challenging task. Here, the authors present an approach whereby an acoustofluidic mechanobiological environment can form reproducible 3D MSC aggregates, allowing for secretome production with high efficiency.
- Ye He
- , Shujie Yang
- & Tony Jun Huang
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Article
| Open AccessMesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice
Major depressive disorder is a major public health problem. Here, the authors illustrate that mesenchymal stromal cells exert antidepressant and anxiolytic effects through a pulmonary vagal→ nucleus tractus solitarius → 5-HT dorsal raphe nucleus neural pathway in murine depression models.
- Jing Huang
- , Weijun Huang
- & Andy Peng Xiang
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Article
| Open AccessEbf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells
CAR cells act as HSC niche cells. Here the authors show that CXCL12 ablation in half CAR cells attracts HSCs from affected CAR cells to intact CAR cells whereas CXCL12 ablation in all CAR cells depletes balanced HSCs producing B cells at high levels.
- Taichi Nakatani
- , Tatsuki Sugiyama
- & Takashi Nagasawa
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Article
| Open AccessPerivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
Hematopoietic stem cells (HSCs) replenish blood cells. Here, Luis et al., identify a feedback mechanism by which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
- Tiago C. Luis
- , Nikolaos Barkas
- & Sten Eirik W. Jacobsen
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Article
| Open AccessA CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans
Extra-intestinal “creeping fat” is a hallmark of Crohn’s disease. Here, using single-cell transcriptomics and lipid metabolomics, the authors identify a subset of mesenchymal stem cells that promote adipogenesis in creeping fat formation.
- Fengfei Wu
- , Fangting Wu
- & Lan Bai
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Article
| Open AccessEfficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis
Using healthy mitochondria to restore impaired mitochondrial homeostasis is a promising therapy for pulmonary fibrosis. Here the authors use joint-engineered mesenchymal stem cells for efficient mitochondrial delivery to injured lung cells, showing a successful mitigation of the disease.
- Ting Huang
- , Ruyi Lin
- & Jianqing Gao
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Article
| Open AccessSingle-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis
Lizards are the closest known relatives of mammals capable of epimorphic tail regrowth. Here, single-cell analysis of regenerating lizard tails reveals a phagocyte-induced fibroblast population contributing to blastema formation and chondrogenesis.
- Ariel C. Vonk
- , Xiaofan Zhao
- & Thomas P. Lozito
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| Open AccessMulti-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1
Mesenchymal stem cells (MSC) are used for immunosuppressive therapy and a uniform source or heterogeneity characterisation is needed. Here the authors use multi-omics to compare human MSC from different sources and ages of donors and show differences in gene expression and immunosuppressive function.
- Yuchen Gao
- , Ying Chi
- & Xiaomin Zhang
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Article
| Open AccessPorous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury
Efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains challenging. Here, the authors fabricate a minimally invasive microneedle device, which provides efficient and sustained extracellular vesicle delivery for spinal cord injury treatment.
- Ao Fang
- , Yifan Wang
- & Xuhua Wang
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Article
| Open AccessHedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration
Successful skeletal muscle regeneration relies on the interplay of multiple cell populations. Here, the authors describe how ciliary Hedgehog signaling coordinates the intercellular crosstalk required to balance wound healing and fatty fibrosis.
- Alessandra M. Norris
- , Ambili Bai Appu
- & Daniel Kopinke
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| Open AccessBone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis
This study identified a new class of skeletal stem cells in the endosteal space of bone marrow, which are abundant in young bone marrow, express Fgfr3 with osteoblast-chondrocyte transitional identities and can turn into bone tumor-making cells.
- Yuki Matsushita
- , Jialin Liu
- & Noriaki Ono
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Article
| Open AccessThe small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors
Stromal cells are essential for intestinal homeostasis. Here the authors describe the phenotype, transcriptional profile and location of stromal cell subsets in the adult murine small intestine and colon lamina propria and demonstrate that these cells derive from Gli1+ precursors present in embryonic day 12.5 intestine.
- Simone Isling Pærregaard
- , Line Wulff
- & William W. Agace
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Article
| Open AccessWHIM Syndrome-linked CXCR4 mutations drive osteoporosis
Using a mouse model harboring a WHIM Syndrome-linked gain-of-function CXCR4 mutation and bone marrow samples from WHIM patients, the authors show that proper CXCR4 signaling termination is essential for bone tissue homeostasis.
- Adrienne Anginot
- , Julie Nguyen
- & Karl Balabanian
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| Open AccessKIAA1199 deficiency enhances skeletal stem cell differentiation to osteoblasts and promotes bone regeneration
The levels of a factor secreted by bone marrow stromal cells, KIAA1199, associate with osteoporotic fracture risk. Here, the authors show that KIAA1199 deficiency can lead to enhanced bone formation, accelerated bone healing, and protects from ovariectomy-induced bone loss.
- Li Chen
- , Kaikai Shi
- & Moustapha Kassem
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| Open AccessAlcam-a and Pdgfr-α are essential for the development of sclerotome-derived stromal cells that support hematopoiesis
The early ontogeny of hematopoietic niches is largely unknown. This article shows that the sclerotome compartment of somites provides Alcam and Pdgfr-α dependent mesenchymal cells that are essential at every step of the development of hematopoiesis.
- Emi Murayama
- , Catherine Vivier
- & Philippe Herbomel
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| Open AccessNanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells
Mesenchymal Stromal Cells are hard to expand whilst retaining immunomodulatory properties due to spontaneous differentiation and ageing in culture. Here, the authors describe a mechanotransductive link between metabolism and functional activity and identify bioactive metabolites to expand functional MSCs at cell therapy scale.
- Ewan A. Ross
- , Lesley-Anne Turner
- & Matthew J. Dalby
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| Open AccessSensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis
Sensory nerves are important for tissue homeostasis. Here the authors show that sensory nerves contribute to Mesenchymal stem cell maintenance via FGF1, mTOR signaling and autophagy.
- Fei Pei
- , Li Ma
- & Yang Chai
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Article
| Open AccessAdipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury
The dynamics of fibroadipogenic progenitors (FAPs) after muscle injury are crucial to ensure efficient regeneration. Here the authors show that a pool of FAPs originates from adipose tissue and are necessary for effective muscle regeneration.
- Quentin Sastourné-Arrey
- , Maxime Mathieu
- & Coralie Sengenès
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Article
| Open AccessDepletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration
Muscle regeneration requires the contribution and communication of various different cell types. Here, Nawaz et al. show that CD206+ macrophages inhibit the secretion of the promyogenic factor follistatin by fibro-adipogenic progenitor cells, impeding myogenesis and muscle regeneration.
- Allah Nawaz
- , Muhammad Bilal
- & Kazuyuki Tobe
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Article
| Open AccessProgrammable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation
Human mesenchymal stem cells differentiate in response to mechanical adhesive interactions in their microenvironment. Here, the authors develop a culture platform that can dynamically mimic the cell-cell and cell-extracellular matrix interactions associated with development and mesenchymal differentiation in vivo.
- Zheng Zhang
- , Baoyong Sha
- & Min Lin
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Article
| Open AccessSexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration
How bone-related sexually dimorphic traits are regulated hasn’t been examined at the stem cell level. Here the authors show that skeletal stem cells (SSC), in female but not male mice, are directly controlled by estrogen signaling, which could be augmented to improve fracture repair.
- Tom W. Andrew
- , Lauren S. Koepke
- & Charles K. F. Chan
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Article
| Open AccessVitamin C epigenetically controls osteogenesis and bone mineralization
For decades vitamin C’s primary function in bone has been attributed to its involvement in collagen synthesis. Here, the authors uncover that vitamin C’s central role in bone is to globally orchestrate osteogenesis via epigenetic mechanisms.
- Roman Thaler
- , Farzaneh Khani
- & Andre J. van Wijnen
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| Open AccessCellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Mesenchymal progenitors (MPs) are fundamental to tissue development and regeneration, however, their embryonic origin is unclear. Single cell-omics coupled with lineage tracing reveal a unique somite-derived MP hierarchy in limb morphogenesis.
- Martin Arostegui
- , R. Wilder Scott
- & T. Michael Underhill
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Article
| Open AccessPeriosteal stem cells control growth plate stem cells during postnatal skeletal growth
Intramembranous and endochondral bone formation have been considered to be independent processes mediated by independent stem cells. Here the authors show that periosteal stem cells participate in both types of bone formation, supporting endochondral formation by producing Ihh.
- Masayuki Tsukasaki
- , Noriko Komatsu
- & Hiroshi Takayanagi
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| Open AccessAdaptive liquid interfaces induce neuronal differentiation of mesenchymal stem cells through lipid raft assembly
In this work the authors report how human mesenchymal stem cells rapidly adapt to dynamic microenvironment through lipid raft in membrane microdomains that direct neurogenesis.
- Xiaofang Jia
- , Jingwen Song
- & Katsuhiko Ariga
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Article
| Open AccessRunx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells
The transcription factors, Runx1 and Runx2 are critical embryonically for generation of HSCs and osteoblasts, respectively. Here the authors show that adult mice lacking Runx1 and Runx2 in HSC-supporting CAR cells displayed an increase in fibrosis with reduced HSCs in bone marrow.
- Yoshiki Omatsu
- , Shota Aiba
- & Takashi Nagasawa
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Article
| Open AccessA FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury
The growth plate cartilage supports long bone growth. Here the authors identify FoxA2+ long term stem cells in the growth plate that are stratified with short term PTHrP+ cells, participate in production of hyaline cartilage, expand in response to trauma, and whose ablation impairs cartilage regeneration.
- Shanmugam Muruganandan
- , Rachel Pierce
- & Andreia M. Ionescu
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Article
| Open AccessCHD7 regulates bone-fat balance by suppressing PPAR-γ signaling
CHD7 is chromatin remodeler and mutations of CHD7 are the main cause of CHARGE syndrome. Here the authors show that conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and pre-osteoblasts leads to a skeletal system development disorder in mice and upregulated PPAR signaling, disrupting the balance between osteogenic and adipogenic differentiation.
- Caojie Liu
- , Qiuchan Xiong
- & Ning Kang
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Article
| Open AccessMesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity
Regulatory T (Treg) cells and mesenchymal stem cells (MSCs) are both cell populations capable of immune tolerance induction. Here the authors show that the transfer of mitochondria from mesenchymal stem cells to allogeneic Treg cells in an HLA-dependent manner results in enhanced immunosuppressive functions of Treg cells.
- Karolina Piekarska
- , Zuzanna Urban-Wójciuk
- & Natalia Maria Marek-Trzonkowska
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Article
| Open AccessDistinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
The pluripotency factor KLF4 has been described as pro-fibrotic or anti-fibrotic in various diseases. Herein, the authors show that during lung fibrosis, these distinct effects can be attributed to mesenchymal cell-type specific functions of KLF4.
- Rachana R. Chandran
- , Yi Xie
- & Daniel M. Greif
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| Open AccessMesenchymal stromal cell apoptosis is required for their therapeutic function
Mesenchymal stromal cells (MSCs) demonstrate therapeutic benefits in multiple diseases, but the mechanisms remain unclear as infused MSCs do not persist in the body. Here, the authors show that MSC apoptosis is an important mechanistic element, as MSCs rendered genetically incapable of apoptosis lose their ability to ameliorate disease.
- Swee Heng Milon Pang
- , Joshua D’Rozario
- & Tracy S. P. Heng
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Article
| Open AccessMechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells
Mesenchymal stem cells adopt differentiation pathways based upon mechanical cues in their environment which change throughout development. Here the authors develop a material and culture system to modify and measure the degree to which cells retain cumulative effects of mechanosensing to explore how cells erase the memory of some cues while locking in memory of others.
- Cheng Zhang
- , Hongyuan Zhu
- & Min Lin
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Article
| Open AccessTNF-α-mediated m6A modification of ELMO1 triggers directional migration of mesenchymal stem cell in ankylosing spondylitis
Abnormal functions of mesenchymal stem cells (MSC) contribute into the pathogenensis of ankylosing spondylitis (AS). Here, the authors show that TNF-α at high concentration induces enhances migration of AS-MSC through METTL14 mediated m6A modification of the ELMO1 3′ UTR.
- Zhongyu Xie
- , Wenhui Yu
- & Huiyong Shen
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Article
| Open AccessSkeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis
Cranial sutures are major growth centers for the skull vault and premature fusion leads to pathological fusion, craniosynostosis. Here the authors isolate Wnt responsive skeletal stem and progenitor cells from sutures, that can be transplanted together with Wnt3a protein to repair craniosynostosis in a mouse model.
- Siddharth Menon
- , Ankit Salhotra
- & Natalina Quarto
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Article
| Open AccessTargeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway
Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.
- Dali Zhang
- , Junlan Huang
- & Yangli Xie
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Article
| Open AccessTCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice
Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.
- Yu-chi Shen
- , Adrienne Niederriter Shami
- & Saher Sue Hammoud
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Article
| Open AccessDirect contribution of skeletal muscle mesenchymal progenitors to bone repair
Bone regeneration involves activation of tissue resident stem cells. Here the authors show that mesenchymal progenitors from skeletal muscle mediate the fibrotic response to bone injury and also contribute to bone repair; processes that are impaired when both muscle and bone are injured.
- Anais Julien
- , Anuya Kanagalingam
- & Céline Colnot
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Article
| Open AccessJanus 3D printed dynamic scaffolds for nanovibration-driven bone regeneration
Fabrication of dynamic, reversible and biocompatible scaffolds with non-invasive external triggers has so far been limited. Here, the authors report on the creation of 3D printed scaffolds with Janus structure that produce nanovibrations when exposed to ultrasound, promoting bone regeneration.
- Sandra Camarero-Espinosa
- & Lorenzo Moroni
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Article
| Open AccessDental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.
- Jan Krivanek
- , Ruslan A. Soldatov
- & Igor Adameyko
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Article
| Open AccessMesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis
Treatment of tuberculosis needs to be taken for several weeks, despite good potency of drugs in vitro. Here, the authors show that mesenchymal stem cells can harbor Mycobacterium tuberculosis providing a niche for evasion of anti-bacterial drugs and cytokines.
- Neharika Jain
- , Haroon Kalam
- & Dhiraj Kumar
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Article
| Open AccessHuman beige adipocytes for drug discovery and cell therapy in metabolic diseases
Methods to generate beige adipocytes from a human cell source are inefficient. Here, the authors present a protocol that efficiently generates beige adipocytes from human adipose-derived stem cells (ADSCs), which have potential utility in therapeutic development relating to metabolic diseases such as type 2 diabetes.
- Amar M. Singh
- , Liang Zhang
- & Stephen Dalton
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Article
| Open AccessCas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice
Human mesenchymal stromal cells are a promising source for cell-based therapies. Here the authors use Cas9 to engineer lines that secrete PDGF-BB and VEFGA for improving wound healing.
- Waracharee Srifa
- , Nina Kosaric
- & Matthew Porteus
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Article
| Open AccessTransit amplifying cells coordinate mouse incisor mesenchymal stem cell activation
Mouse incisor growth depends upon mesenchymal stromal cells (MSCs) and transit amplifying cells (TACs). Here the authors describe a distinct population of MSCs that is maintained by TACs through Dlk1 ligand and that contribute to MTACs and mesenchymal lineages including dental pulp and odontoblasts.
- Jemma Victoria Walker
- , Heng Zhuang
- & Bing Hu