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Project description:Generation of Human Expandable Progenitors with Limb-Bud Features via Chemically Induced Dedifferentiation
| PRJNA1020587 | ENA
Project description:Here, we introduce a novel chemically induced dedifferentiation approach that reverses the cellular development from a differentiated state to progenitor state with reduced senescence features, conferring the generation of limb bud progenitors from human adult mesenchymal stromal cells and dermal fibroblasts. These chemically induced limb bud cells (hCiLB cells) show a high degree of transcriptomic similarity to human embryonic limb bud cells. We found that hCiLB cells can undergo extensive expansion, while maintaining population homogeneity and long-term self-renewal capacity. Moreover, hCiLB cells exhibit increased osteochondrogenic differentiation ability than their parental cells, providing a new platform for the development of authentic articular cartilage. These results also highlight a potential therapeutic approach for the repair of damaged human tissues through reversal of developmental pathways from mature cells to expandable progenitor cells.
2024-09-01 | GSE243929 | GEO
Project description:Here, we introduce a novel chemically induced dedifferentiation approach that reverses the cellular development from a differentiated state to progenitor state, conferring the generation of limb bud progenitors from human adult mesenchymal stromal cells and dermal fibroblasts. These chemically induced limb bud cells (hCiLB cells) show a high degree of transcriptomic similarity to human embryonic limb bud cells. We found that hCiLB cells can undergo extensive expansion, while maintaining population homogeneity and long-term self-renewal capacity. Moreover, hCiLB cells exhibit increased osteochondrogenic differentiation ability than their parental cells, providing a new platform for the development of authentic articular cartilage. These results also highlight a potential therapeutic approach for the repair of damaged human tissues through reversal of developmental pathways from mature cells to expandable progenitor cells.
2024-09-01 | GSE243930 | GEO
Project description:Generation of Human Expandable Limb Bud Cells via Chemically Induced Dedifferentiation Strategy [scRNA-seq]
| PRJNA1020590 | ENA
Project description:Generation of Human Expandable Limb Bud Cells via Chemically Induced Dedifferentiation Strategy [bulk RNA-seq]
| PRJNA1020589 | ENA
Project description:Current kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney's collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of the adult kidney's collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Applying an efficient gene editing strategy to remove RET activity, we demonstrate genetically modified UB organoids can model congenital anomalies of kidney and urinary tract. Taken together, these platforms will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting duct system.
| S-EPMC8206157 | biostudies-literature
Project description:BackgroundCell sheet fabrication for articular cartilage regenerative medicine necessitates a large number of chondrocytes of consistent quality as a cell source. Previously, we have developed human-induced pluripotent stem cell (iPSC)-derived expandable PRRX1+ limb-bud mesenchymal cells (ExpLBM) with stable expansion and high chondrogenic capacity, while in this study; our ExpLBM technology was combined with cell sheet engineering to assess its potential as a stable cell source for articular cartilage regeneration.MethodsExpLBM cells derived from human-induced pluripotent stem cells (hiPSCs), including 414C2 and Ff-KVs09 (HLA homozygous), were seeded onto a culture plate and two-dimensional chondrogenic induction (2-DCI) was initiated. After 2-DCI, ExpLBM-derived chondrocytes were stripped and transferred to temperature-responsive culture inserts and the chondrocyte sheets were histologically examined or transplanted into osteochondral knee defects of immunodeficient rats.ResultsImmunohistochemistry revealed that ExpLBM-derived cell sheets were positive for Safranin O, COL2, and ACAN but that they were negative for COL1 and RUNX2. Furthermore, the engrafted tissues in osteochondral knee defects in immunodeficient rats were stained with SafO, human VIMENTIN, ACAN, and COL2.ConclusionsThe present study is the first to report the chondrocyte sheet fabrication with hiPSC-derived cell source. hiPSC-derived ExpLBM would be a promising cell source for cell sheet technology in articular cartilage regenerative medicine.
| S-EPMC9960196 | biostudies-literature
Project description:ObjectiveSepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action.MethodsThe sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. In vitro, ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome.ResultsThe mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells.ConclusionsLBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.
| S-EPMC7847343 | biostudies-literature
Project description:Identification of progenitors populations through FACS in the early limb buds (E10.5 and E11.5) followed by RNA-seq. These populations showed distinct signalling pathways, that were confirmed in vitro and in vivo.
2019-05-16 | GSE116115 | GEO
Project description:Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.
| S-EPMC4335807 | biostudies-literature