Project description:Adult tissue stem cells (SCs) reside in niches, which through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single cell RNA-sequencing, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage-tracing, temporal single cell analyses and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged uni-lineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: Some progenitors specify lineages immediately; others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.
Project description:Adult tissue stem cells (SCs) reside in niches, which through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single cell RNA-sequencing, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage-tracing, temporal single cell analyses and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged uni-lineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: Some progenitors specify lineages immediately; others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.
Project description:Adult tissue stem cells (SCs) reside in niches, which through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single cell RNA-sequencing, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage-tracing, temporal single cell analyses and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged uni-lineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: Some progenitors specify lineages immediately; others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.
Project description:Cancer cell behaviour is strongly influenced by the surrounding cellular environment, making the characterization of the local tumour microenvironment (or niche) a fundamental question in tumour biology. To date, a direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue is difficult to achieve, especially at early micro-metastatic stages and for low frequency niche populations. Here we present the strategy whereby metastatic cancer cells release a cell-penetrating fluorescent protein that is efficiently taken up by neighbouring cells, allowing spatial identification of the local metastatic cellular environment within the whole tissue. Notably, this strategy can be used to follow metastatic niches from early micro-metastasis to late macro-metastasis, allowing temporal resolution. Moreover, the presence of low represented niche cells can be detected and characterized among the bulk tissue. To highlight its potential, we have used this niche-labelling strategy to study the lung metastatic environment of breast cancer cells. We uncover the presence of lung parenchymal cells within the metastatic niche where lung epithelial cells show stem cell-like features with expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. Moreover, lung epithelial cells can be directly perturbed by cancer cells in ex vivo co-culture assays and support their growth. In summary, here we describe a novel labelling system that enables spatial resolution of the metastatic microenvironment and provide evidence that the tissue cellular environment surrounding metastatic growth is characterized by undifferentiated features. The data highlight the significant potential of this method as a platform for new discoveries.
Project description:Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%â99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. doi:10.1016/j.cell.2016.06.011 BioProject: PRJNA319573, Study: SRP073808, Bulk and single-cell RNA-seq, and ATAC-seq of of H7 human embryonic stem cells (ESC) and in vitro derived 10 diffrerent mesoderm progenitors from H7-ESC
Project description:Bulk RNA-seq of B-ALL cells cocultured with bone marrow-mesenchymal stem cells (BM-MSC) identified that B-ALL acquire epithelial-mesenchymal transition (EMT) properties by interacting with primary bone marrow-mesenchymal stem cells (BM-MSC) and scRNA-seq dissected the hybrid cluster of adherent B-ALL (Adh B-ALL) harboring B-ALL and BM-MSC features induced by EMT program
Project description:Cell samples of undifferentiated human umbilical cord mesenchymal stem cells (1-3) and cells that have been cultured in smooth muscle differentiation medium for 6 hours (4-6) and 24 hours (7-9) were collected and subjected to miRNA array. Exploration of miRNA involved smooth muscle differentiation mechanism would offer potential therapeutic choices for improving performance of vascular grafts engineered with umbilical cord mesenchymal stem cells.