Gli1 Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an Important Cellular Therapeutic Target
Bhaskar Chanda Stem Cell Schneider and colleagues show that Gli1+ bone marrow mesenchymal stromal cells are an important source of fibrotic cells during bone marrow fibrosis and that targeting of Gli proteins with GANT61 holds promise for amelioration of this disease.
Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions
Bhaskar Chanda Stem Cell Li et al. interrogate the transcriptomes of over 2,000 fetal germ cells (FGCs) and their gonadal niche cells from male and female human embryos using single-cell RNA-seq analysis. They provide insights into the developmental trajectories and heterogeneity in FGCs over a wide range of developmental stages.
Bhaskar Chanda Stem Cell The molecular equivalence of ESCs and EGCs remains incompletely understood. Choi et al. show that ESCs and EGCs are highly similar and that sex rather than cell type drives the transcriptional and epigenetic differences observed between individual cell lines. Female-specific hypomethylation is partially due to upregulation of the X-linked MAPK phosphatase DUSP9.
H3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer Embryos
Bhaskar Chanda Stem Cell Hörmanseder et al. find that persistent memories of transcriptional activity in donor cell identity genes present a barrier to cell-fate reprogramming following nuclear transfer. They show that reducing H3K4 methylation in donor cells reduces transcriptional memory and improves the development of embryos derived by nuclear transfer.
Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling
Bhaskar Chanda Stem Cell Kotton and colleagues show that carefully timed regulation of Wnt signaling can direct human pluripotent cells to differentiate rapidly into functional airway epithelial organoids with many potential applications in disease modeling, drug screening, and precision medicine, and for diseases such as cystic fibrosis.
Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States
Bhaskar Chanda Stem Cell Collier et al. use profiling to identify cell surface proteins that are specific for naive versus primed human pluripotent cells and then use them to isolate and characterize live naive cells arising during primed-to-naive resetting.
Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution
Bhaskar Chanda Stem Cell CLEVER-seq is a single-cell, single-base resolution whole-genome 5fC-sequencing technology. CLEVER-seq reveals intrinsic 5fC heterogeneity in mouse early embryos, EpiSCs, and ESCs and dissects its highly patterned genomic distributions. During mouse pre-implantation development, 5fC shows parental-specific signatures, and promoter 5fC production precedes the upregulation of corresponding gene expression.
Bhaskar Chanda Stem Cell Lucchetta and Ohlstein describe an unexpected mechanism of stem cell replacement in the Drosophila intestine. They found that in some situations where many stem cells are lost, they can be replaced through a process of ploidy reduction, or amitosis, of differentiated polyploid cells to regenerate functional stem cells.
Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
Bhaskar Chanda Stem Cell Ambrosi, Schulz, and colleagues define a stem cell-like population that gives rise to osteogenic progeny and promotes hematopoietic reconstitution. Aging and high-fat diet reprogram the mesenchymal lineage to preferentially give rise to adipogenic cells that impair reconstitution and bone fracture healing. Bone tissue repair is fully restored by DPP4 inhibition.
Bhaskar Chanda Stem Cell Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration.