Stem Cells

Adult muscle stem cells (MuSCs) are known to replicate upon activation before differentiating and fusing to regenerate myofibers. It is unclear whether MuSC differentiation is intrinsically linked to cell division, which has implications for stem cell population maintenance. We use single-cell RNA-sequencing to identify transcriptionally diverse subpopulations of MuSCs after 5 days of a growth stimulus in adult muscle. Trajectory inference in combination with a novel mouse model for tracking MuSC-derived myonuclei and in vivo labeling of DNA replication revealed an MuSC population that exhibited division-independent differentiation and fusion...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Polymorphonuclear neutrophils (PMNs), the predominant immune cell type in humans, have long been known as first-line effector cell against bacterial infections mainly through phagocytosis and production of reactive oxygen species (ROS). However, recent research has unveiled novel and pivotal roles of these abundant but short-lived granulocytes in health and disease. Human mesenchymal stromal/stem cells (MSCs), renowned for their regenerative properties and modulation of T lymphocytes from effector to regulatory phenotypes, exhibit complex and context-dependent interactions with PMNs...

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation...

Increased fructose consumption has been elucidated to contribute to metabolic diseases. Bone is a dynamic organ that undergoes constant remodeling. However, the effects of fructose on bone health are still in dispute. Here, we identified fructose deteriorated bone mineral density while promoting the abundance of bone marrow adipose tissue. Fructose remarkably promoted the bone marrow mesenchymal stem cells' (BMMSCs) adipogenic commitment at the expense of osteogenic commitment. Fructose boosted the glycolysis of BMMSCs and inhibited phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), which played a crucial role in bone-fat alteration...

BACKGROUND: The use of human umbilical cord mesenchymal stem cells (UC-MSCs) has shown promise in improving the pathophysiological characteristics of rats with chronic obstructive pulmonary disease (COPD). However, more research is needed to understand the exact mechanism behind their therapeutic effects and their impact on lung microbiota. METHODS: To investigate this, rats were randomly assigned to one of three groups: Control, COPD+vehicle, and COPD+UC-MSCs group...

Somatic cells that have been partially reprogrammed by the factors Oct4, Sox2, Klf4, and cMyc (OSKM) have been demonstrated to be potentially tumorigenic in vitro and in vivo due to the acquisition of cancer-associated genomic alterations and the absence of OSKM clearance over time. In the present study we obtained partially reprogrammed, SSEA1-negative cells by transducing murine hepatocytes with Δ1Δ3-deleted adenoviruses that expressed the four OSKM factors. We observed that, under long-term 2D and 3D culture conditions, hepatocytes could be converted into LGR5-positive cells with self-renewal capacity that was dependent on three cross-signaling pathways: IL6/Jak/Stat3, LGR5/R-spondin, and Wnt/β-catenin...

It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction (MI), being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos)...

Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) have unique characteristics where they can both contribute to all three germ layers in vivo and self-renewal indefinitely in vitro. Post-translational modifications of proteins, particularly by the ubiquitin proteasome system (UPS), controls cell pluripotency, self-renewal, and differentiation. A significant number of UPS members (mainly ubiquitin ligases) regulate pluripotency and influence ESC differentiation with key elements of the ESC pluripotency network (including the "master" regulators NANOG and OCT4) being controlled by ubiquitination...

Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system...

Acute graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication following allogeneic hematopoietic cell transplantation (HCT). Mesenchymal stromal cells (MSCs), rare precursors found in all body tissues, possess immunosuppressive properties and can inhibit alloreactivity both in vitro and in vivo. Two decades ago, we introduced bone marrow-derived (BM) MSCs as a novel therapy for acute GVHD. While some patients responded to BM-MSCs, the response was not universal. Commercially available BM-MSCs are now used for acute GVHD treatment in Canada, Japan, and New Zealand...

Chronic inflammation and dysregulated repair mechanisms after epithelial damage have been implicated in COPD. However, the lack of ex vivo-models that accurately reflect multicellular lung tissue hinders our understanding of epithelial-mesenchymal interactions in COPD. Through a combination of transcriptomic and proteomic approaches applied to a sophisticated in vitro iPSC- alveolosphere with fibroblasts model, epithelial-mesenchymal cross-talk was explored in COPD and following SARS-CoV-2 infection. These experiments profiled dynamic changes at single-cell level of the SARS-CoV-2-infected alveolar niche that unveiled the complexity of aberrant inflammatory responses, mitochondrial dysfunction, and cell death in COPD, which provides deeper insights into the accentuated tissue damage/inflammation/remodeling observed in patients with SARS-CoV-2 infection...

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30 to 80% experiencing it within two years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant Leukemic Stem Cells (LSCs)...

No abstract text is available yet for this article.

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication...

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). The present study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western Blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, rat anterior cruciate ligament transection OA model were used to evaluate the effects of SSCs on osteoblast necroptosis in vivo...

Neurogenesis begins with neural stem cells undergoing symmetric proliferative divisions to expand and then switching to asymmetric differentiative divisions to generate neurons in the developing brain. Chromatin regulation plays a critical role in this switch. Histone lysine-specific demethylase LSD1 demethylates H3K4me1/2 and H3K9me1/2 but the mechanisms of its global regulatory functions in human neuronal development remain unclear. We performed genome-wide ChIP-seq of LSD1 occupancy, RNA-seq, and Histone ChIP-seq upon LSD1 inhibition to identify its repressive role in human neural stem cells...

β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C>T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation...