Identification of LRP1 and CD13 expressing human periosteal cells for stem cell-mediated bone repair
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PROVIDER: PRJNA1157865 | ENA |
REPOSITORIES: ENA
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Project description:Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, PDPN and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs (BM-SSCs), selectively expressed newly identified markers, LRP1 and CD13. Single-cell analysis of mouse periosteum further supported the preferential expression of LRP1 and CD13 in Prx1 P-SSCs. These LRP1CD13 human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. In addition, LRP1CD13 human P-SSCs are maintained in vitro and self-renew in vivo upon transplantation into bone injuries in mice. When Lrp1 was conditionally deleted in Prx1-lineage cells, it led to severe bone deformity, short statue, and periosteal defects. By contrast, local treatment with a LRP1 agonist at the injury sites induced early P-SSC proliferation and bone healing. Thus, human periosteum contains unique osteochondrogenic stem cell subsets, and these P-SSCs express specific markers, LRP1 and CD13, with regulatory mechanism through LRP1 that enhances P-SSC function and bone repair.
2024-11-04 | GSE276574 | GEO
Project description:Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, PDPN and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs (BM-SSCs), selectively expressed newly identified markers, LRP1 and CD13. Single-cell analysis of mouse periosteum further supported the preferential expression of LRP1 and CD13 in Prx1 P-SSCs. These LRP1CD13 human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. In addition, LRP1CD13 human P-SSCs are maintained in vitro and self-renew in vivo upon transplantation into bone injuries in mice. When Lrp1 was conditionally deleted in Prx1-lineage cells, it led to severe bone deformity, short statue, and periosteal defects. By contrast, local treatment with a LRP1 agonist at the injury sites induced early P-SSC proliferation and bone healing. Thus, human periosteum contains unique osteochondrogenic stem cell subsets, and these P-SSCs express specific markers, LRP1 and CD13, with regulatory mechanism through LRP1 that enhances P-SSC function and bone repair.
2024-11-04 | GSE278165 | GEO
Project description:Identification of LRP1 and CD13 expressing human periosteal cells for stem cell-mediated bone repair [human scRNA-seq]
| PRJNA1165790 | ENA
Project description:To study the effect of expression of CD13/CD33 on the pathogenesis of B-cell acute lymphoblastic (B-ALL), we collected samples from 4 CD13/CD33-positive and 4 CD13/CD33-negative B-ALL patients and performed RNA-seq.
2023-12-31 | GSE197180 | GEO
Project description:To study the effect of expression of CD13/CD33 on the pathogenesis of B-cell acute lymphoblastic (B-ALL), we collected samples from 4 CD13/CD33-positive and 4 CD13/CD33-negative B-ALL patients and performed RNA-seq.
2023-12-31 | GSE197178 | GEO
Project description:Primary mesenchymal CD105+CD90+CD13- and CD105+CD90+CD13+ populations from human lung were isolated and characterized using bulk population mRNA sequencing to understand differences between these populations.
2021-12-24 | GSE173738 | GEO
Project description:The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To directly address the function of myeloid CD13 we created a CD13 null mouse and assessed the responses of purified primary macrophages or dendritic cells from wild type and CD13 null animals in cell assays and inflammatory disease models where CD13 has been previously implicated. We find that mice lacking CD13 develop normally with normal hematopoietic profiles. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation and antigen presentation that we tested, but may contribute to adhesion to endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 wild type and null macrophages argue against compensatory mechanisms. Analysis of the dataset with Ingenuity Pathway Analysis software did not suggest that loss of CD13 resulted in a purturbation of any specific biological pathways, processes or networks. Therefore, while CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of both normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis or myeloid cell function.
2010-09-30 | GSE20985 | GEO
Project description:The periosteum contains cells which function as a reservoir of stem cells and progenitors and contribute to cortical expansion during growth, cortical bone homeostasis and repair. However, the local or paracrine factors that govern stem cell renewal and differentiation within the periosteal niche remains elusive. Cathepsin K (Ctsk) together with additional cell surface markers marks a subset of stem cells in the periosteum (PSC) which possess self-renewal ability and inducible multipotency. These PSCs produce osteoblasts mediating periosteal bone formation and fracture repair. Sfrp4 is expressed in periosteal Ctsk-lineage cells and using CtskCre mice that are either wild type or Sfrp4-/-, we report here that Sfrp4 deletion decreases the pool of PSCs, impairs their self-renewal, their ability to give rise to their derivatives and their clonal multipotency for differentiation into osteoblasts and chondrocytes in vitro and formation of bone organoids in vivo. Bulk RNA sequencing analysis in Ctsk-lineage PSCs demonstrated that Sfrp4 deletion leads to downregulation of signaling pathways associated with skeletal development, positive regulation of bone mineralization and wound healing. Sfrp4 deletion hampers the Ctsk-lineage PSC response and recruitment after bone injury and leads to an impaired periosteal response. Periosteal Ctsk-lineage cells respond to PTH(1-34) treatment with an increase in the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, bone histomorphometry analysis showed that in the absence of Sfrp4, PTH(1-34)-dependent increase in cortical thickness, periosteal bone formation is markedly impaired.
2024-08-13 | GSE236686 | GEO
Project description:The phases of fracture healing have been well characterized. However, the exact source and genetic profile of the skeletal progenitors that participate in bone repair is somewhat unclear. Sox9 expression in skeletal elements precedes bone and cartilage formation and a Sox9+ cell type is retained in the adult periosteum. We hypothesized that Sox9+ periosteal cells are multipotent skeletal progenitors normally participating in fracture repair. To test this hypothesis we used tamoxifen (TM)-mediated lineage tracing of Sox9+ cells in Sox9CreErt2:Td-Tomato mice. TM injection indelibly labels Sox9+ cells and all their descendants with the fluorescent reporter protein Td-Tomato. Intact mouse femora were harvested 2 weeks after TM injection and analyzed by histology and immunostaining and RNA sequencing, to evaluate the skeletal distribution and gene expression profile of Td-Tomato positive cells in the adult femur. To assess the role of these cells in fracture repair, mice underwent a closed mid-diaphyseal femoral fracture and their hind limbs were harvested at 3, 9 or 56 days post-fracture to assess the contribution of Sox9+ and Td-tomato+ cells in the fracture healing process. In the intact adult mouse femur, Td-Tomato-labelled cells were observed in articular and growth plate cartilage where Sox9 is known to be expressed, but also in the primary spongiosa, periosteum, and endosteum. RNA sequencing and subsequent analysis showed that Td-Tomato positive periosteal cells were enriched in Sox9 transcripts, and transcripts for various osteogenic and chondrocyte specific genes. In a femoral fracture model, we showed that pre-labeled Td-Tomato positive descendent cells were mobilized during the fracture repair process, expanding and migrating towards the fracture site 3 days post-fracture. Here, Td-Tomato positive cells differentiate into chondrocytes and osteoblasts in the soft and hard callus, respectively, 9 days post-fracture. By 2 months post-fracture, descendants of the original Sox9 labelled cell population were prevalent in the cortex and periosteum, and amongst the differentiated osteocyte population embedded within the cortical bone. Thus, a Sox9+ progenitor population resides in the adult periosteum. Fate tracing shows that these cells likely play a substantial role in repair of the fractured femur giving rise to chondrocytes, osteoblasts and mature cortical osteocytes. To our knowledge this is the first report of this Sox9+ cell population in the periosteum of the adult long bone. Taken together with developmental studies on skeletal formation, our data suggest that Sox9+ osteochondroprogenitors play a continuous role in skeletal formation throughout life.
2018-04-25 | GSE98587 | GEO
Project description:Clostridioides difficile CD13 Genome sequencing and assembly
| PRJNA85683 | ENA