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Gli1-expressing stromal cells are highly reparative precursors of long-lived chondroprogenitors in the fetal murine limb

ABSTRACT: Single-cell RNA sequencing of cells dissociated from Hindlimb at E14.5 embryos to identify how catch-up growth happens during injury and to show transcriptional identities of contributors to chondrocytes in p21-overexpression induced injury model.

ORGANISM(S): Mus musculus

PROVIDER: GSE273538 | GEO | 2025/09/26

REPOSITORIES: GEO

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Gli1-expressing stromal cells are highly reparative precursors of long-lived chondroprogenitors in the fetal murine limb

Project description:Single-nuclei RNA sequencing of cells dissociated from Hindlimb (femur and tibia, from RZ to PHT Region) from E16.5 embryos to identify how catch up grpwuth happens during injury and to to show transcriptional identities of contributors to chondrocytes in p21-overexpression induced injury in unilateral models.

2025-09-26 | GSE273540 | GEO

In vivo characterization of Linc-p21 reveals functional cis-regulatory DNA elements

Project description:We have sequenced wildtype and mutant heart, liver, lung, and hindlimb from E14.5 embryos of the mutant lncRNA strain Trp53cor1tm1.1Vlcg (lincp21), and performed a massively parallel reporter assay (MPRA) in mouse myoblast cells (C2C12).

2016-08-11 | GSE73472 | GEO

Deciphering the genetics of mammalian limb growth

Project description:We have used DGE-SAGE, a digital transcriptomics tool, to determine the expression profile of E14.5 mouse forelimbs and hindlimbs. The forelimb, hindlimb developmental lag combined with the analysis of these datasets allow us a better insight into the dynamics of the limb growth genetic network, in particular the characterisation of genes that are differentially expressed and are putative modulators of limb growth and or candidates for limb malformation syndromes. Conclusions: The datasets and results presented in this study allow us to extend the current knowledge of the limb development and constitute an extremely relevant resource for research into the genetics of organ growth and thus ontogenesis. DGE-SAGE expression profiles for E14.5 mouse forelimb and hindlimb

2014-01-01 | E-GEOD-41222 | biostudies-arrayexpress

Proteomics analysis of tibialis anterior muscle and descending thoracic aorta from Mustn1 whole-body knockout mice and wild-type littermates

Project description:Skeletal muscle is a highly adaptive tissue that changes with many physiological stimuli and is composed of many cell types. Upon muscle injury, the concerted action of these cells is required to proceed through the process of inflammation, extracellular matrix remodeling, and restoration of function. To uncover novel genes and molecular pathways important for skeletal muscle remodeling and regeneration, we used a mouse hindlimb unloading and reloading protocol, and performed transcriptomics analysis. This study focuses on the microprotein Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang), whose gene expression is increased in muscle at the onset of hindlimb reloading, exercise, and injury. We generated a whole-body Mustn1 knockout mouse model and performed proteomics analysis of muscle and aorta.

2024-05-24 | PXD046610 | Pride

Transcriptomes of mesonephros- vs. ovary-derivd Gli1+ cells

Project description:This goal of this microarray analysis is to determine whether the mesonephros-derived theca cells exhibt a different gene expression profile from that of the whole theca cell population The mesonephros-derived (n=3, Tamoxifen at E12.5, E14.5 and E16.5) and the neonatal ovary-derived Gli1-positive cells (n=3 Tamoxifen at P1-3 via lactating dams), were isolated from the adult ovaries of Gli1-CreERT2; Rosa-LSL-tdTomato mice at 2 months of age and were sorted by FACS

2015-04-28 | E-GEOD-66104 | biostudies-arrayexpress

Coordinating Tissue Regeneration through TGF-β Activated Kinase 1 (TAK1) In-activation and Re-activation

Project description:Our study reveals up-regulation of the TAK1 pathway when compared with the uninjured hindlimb in our model of trauma-induced heterotopic ossification (tHO) consisting of hindlimb Achilles’ tendon transection with dorsal burn injury.

2019-06-10 | GSE126118 | GEO

HIV-1 Infection of Long-Lived Hematopoietic Precursors In Vitro and In Vivo.

Project description:Latent reservoirs in human-immunodeficiency-virus-1 (HIV-1)-infected individuals represent a major obstacle in finding a cure for HIV-1. Hematopoietic stem and progenitor cells (HSPCs) have been described as potential HIV-1 targets, but their roles as HIV-1 reservoirs remain controversial. Here we provide additional evidence for the susceptibility of several distinct HSPC subpopulations to HIV-1 infection in vitro and in vivo. In vitro infection experiments of HSPCs were performed with different HIV-1 Env-pseudotyped lentiviral particles and with replication-competent HIV-1. Low-level infection/transduction of HSPCs, including hematopoietic stem cells (HSCs) and multipotent progenitors (MPP), was observed, preferentially via CXCR4, but also via CCR5-mediated entry. Multi-lineage colony formation in methylcellulose assays and repetitive replating of transduced cells provided functional proof of susceptibility of primitive HSPCs to HIV-1 infection. Further, the access to bone marrow samples from HIV-positive individuals facilitated the detection of HIV-1 gag cDNA copies in CD34+ cells from eight (out of eleven) individuals, with at least six of them infected with CCR5-tropic HIV-1 strains. In summary, our data confirm that primitive HSPC subpopulations are susceptible to CXCR4- and CCR5-mediated HIV-1 infection in vitro and in vivo, which qualifies these cells to contribute to the HIV-1 reservoir in patients.

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Short-lived calcium carbonate precursors observed in situ via Bullet-dynamic nuclear polarization.

Project description:The discovery of (meta)stable pre-nucleation species (PNS) challenges the established nucleation-and-growth paradigm. While stable PNS with long lifetimes are readily accessible experimentally, identifying and characterizing early-stage intermediates with short lifetimes remains challenging. We demonstrate that species with lifetimes ≪ 5 s can be characterized by nuclear magnetic resonance spectroscopy when boosted by 'Bullet' dynamic nuclear polarization (Bullet-DNP). We investigate the previously elusive early-stage prenucleation of calcium carbonates in the highly supersaturated concentration regime, characterizing species that form within milliseconds after the encounter of calcium and carbonate ions and show that ionic pre-nucleation species not only govern the solidification of calcium carbonates at weak oversaturation but also initiate rapid precipitation events at high concentrations. Such, we report a transient co-existence of two PNS with distinct molecular sizes and different compositions. This methodological advance may open new possibilities for studying and exploiting carbonate-based material formation in unexplored parts of the phase space.

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Mustn1 is a smooth muscle cell-secreted micropeptide that modulates skeletal muscle extracellular matrix composition

Project description:We show that Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang) is highly expressed in skeletal muscle during the early stages of hindlimb reloading. Mustn1 expression is transiently elevated in mouse and human skeletal muscle in response to intense exercise, resistance exercise, or injury. We find that Mustn1 expression is highest in smooth muscle-rich tissues, followed by skeletal muscle fibers. Muscle from heterozygous Mustn1-deficient mice exhibit differences in gene expression related to the extracellular matrix and cell adhesion, compared to wild-type littermates. Mustn1-deficient mice have normal muscle and aorta function and whole-body glucose metabolism. Loss of Mustn1 in vascular smooth muscle cells does not affect their proliferative or migratory functions. We show that Mustn1 can be secreted from smooth muscle cells, and that it is present in arterioles of the muscle microvasculature and in muscle interstitial fluid, in particular during the hindlimb reloading phase. Proteomics analysis of muscle from Mustn1-deficient mice confirms differences in extracellular matrix composition, and female mice display higher collagen content after chemically induced muscle injury compared to wild-type littermates.

2024-05-23 | PXD047169 | Pride

The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1<sup>+</sup> precursors.

Project description:The intestinal lamina propria contains a diverse network of fibroblasts that provide key support functions to cells within their local environment. Despite this, our understanding of the diversity, location and ontogeny of fibroblasts within and along the length of the intestine remains incomplete. Here we show that the small and large intestinal lamina propria contain similar fibroblast subsets that locate in specific anatomical niches. Nevertheless, we find that the transcriptional profile of similar fibroblast subsets differs markedly between the small intestine and colon suggesting region specific functions. We perform in vivo transplantation and lineage-tracing experiments to demonstrate that adult intestinal fibroblast subsets, smooth muscle cells and pericytes derive from Gli1-expressing precursors present in embryonic day 12.5 intestine. Trajectory analysis of single cell RNA-seq datasets of E12.5 and adult mesenchymal cells suggest that adult smooth muscle cells and fibroblasts derive from distinct embryonic intermediates and that adult fibroblast subsets develop in a linear trajectory from CD81+ fibroblasts. Finally, we provide evidence that colonic subepithelial PDGFRαhi fibroblasts comprise several functionally distinct populations that originate from an Fgfr2-expressing fibroblast intermediate. Our results provide insights into intestinal stromal cell diversity, location, function, and ontogeny, with implications for intestinal development and homeostasis.

| S-EPMC10121680 | biostudies-literature

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