- Selected publications
- Complete list of publications
- Patents
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1. Complete list of publications
2025
de Faria FW, Riedel NC, Münter D, Interlandi M, Göbel C, Altendorf L, Richter M, Melcher V, Thomas C, Roy R, Schoof M, Bedzhov I, Moreno N, Graf M, Hotfilder M, Holdhof D, Hartmann W, Bruns AK, Brentrup A, Liesche-Starnecker F, Maerkl B, Sandmann S, Varghese J, Dugas M, Pinto PH, Balbach ST, Lu IN, Rossig C, Soehnlein O, Canak A, Ebinger M, Schuhmann M, Schittenhelm J, Frühwald MF, Schüller U, Albert TK, Walter C, Bruder JM, Kerl K.
Nature Communications 2025
https://doi.org/10.1038/s41467-025-60442-9
Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations – RG-like, NProg-like and NB-like – positioned within a putative neurodevelopmental hierarchy. We reveal PDGFRβ+ pericytes as key communication partners in the TME, contributing to stem cell signaling through extracellular matrix-mediated interactions with tumor cells. PDGF signaling is upregulated in chemoresistant RG-like cells in vivo and plays a role in recruiting pericytes to ETMR TME by finalizing a signaling cascade which promotes the differentiation of non-malignant radial glia cells, derived from our 3D model, into pericyte-like cells. Selective PDGFR-inhibition blocked the lineage differentiation into pericytes in vitro and reduced the tumor cell population in vivo. Targeting ETMR-pericyte interactions in the TME presents a promising therapeutic approach.
Prit D, Jaitly S, Govindasamy N, Ranga A, Bedzhov I.
Methods Mol Biol. 2025
https://doi.org/10.1007/7651_2025_646
The cellular dynamics during peri-implantation embryogenesis and the concurrent interactions at the embryo-maternal interface are inherently difficult to study due to intrauterine development in mammals. To model certain aspects of these processes in vitro, we have generated a biomimetic environment resembling the mechanical properties of the murine uterine stroma. Here we describe a step-by-step methodology for 3D culture of mouse embryos and ectoplacental cone explants in synthetic hydrogels that allow ex utero trophoblast invasion.
Chen R, Fan R, Bedzhov I.
STAR Protocols 2025
https://doi.org/10.1016/j.xpro.2025.103813
Embryonic dormancy (diapause) is a reproductive adaptation that allows some mammalian species to prolong pregnancy and delay birth by temporarily suspending embryonic development just before implantation. Here, we present a step-by-step protocol for inducing and maintaining embryonic diapause in mice by tamoxifen administration or ovariectomy. We describe steps for setting up mouse matings, the administration of pharmacological compounds, the surgical procedure for the removal of the ovaries, postoperative care, and the isolation of dormant embryos. We then describe procedures for triggering exit from diapause by administration of β-estradiol and the subsequent isolation of reactivated embryos.
Hou Y, Nie Z, Jiang Q, Velychko S, Heising S, Bedzhov I, Wu G, Adachi K, Scholer HR.
Elife 2025
https://doi.org/10.7554/elife.100735
During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
2024
de Faria FW, Riedel NC, Münter D, Interlandi M, Göbel C, Altendorf L, Richter M, Melcher V, Thomas C, Roy R, Schoof M, Bedzhov I, Moreno N, Graf M, Hotfilder M, Holdhof D, Hartmann W, Bruns AK, Brentrup A, Liesche-Starnecker F, Maerkl B, Sandmann S, Varghese J, Dugas M, Pinto PH, Balbach ST, Lu IN, Rossig C, Soehnlein O, Canak A, Ebinger M, Schuhmann M, Schittenhelm J, Frühwald MF, Schüller U, Albert TK, Walter C, Bruder JM, Kerl K.
Nature Communications 2025
https://doi.org/10.1038/s41467-025-60442-9
Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations – RG-like, NProg-like and NB-like – positioned within a putative neurodevelopmental hierarchy. We reveal PDGFRβ+ pericytes as key communication partners in the TME, contributing to stem cell signaling through extracellular matrix-mediated interactions with tumor cells. PDGF signaling is upregulated in chemoresistant RG-like cells in vivo and plays a role in recruiting pericytes to ETMR TME by finalizing a signaling cascade which promotes the differentiation of non-malignant radial glia cells, derived from our 3D model, into pericyte-like cells. Selective PDGFR-inhibition blocked the lineage differentiation into pericytes in vitro and reduced the tumor cell population in vivo. Targeting ETMR-pericyte interactions in the TME presents a promising therapeutic approach.
Prit D, Jaitly S, Govindasamy N, Ranga A, Bedzhov I.
Methods Mol Biol. 2025
https://doi.org/10.1007/7651_2025_646
The cellular dynamics during peri-implantation embryogenesis and the concurrent interactions at the embryo-maternal interface are inherently difficult to study due to intrauterine development in mammals. To model certain aspects of these processes in vitro, we have generated a biomimetic environment resembling the mechanical properties of the murine uterine stroma. Here we describe a step-by-step methodology for 3D culture of mouse embryos and ectoplacental cone explants in synthetic hydrogels that allow ex utero trophoblast invasion.
Chen R, Fan R, Bedzhov I.
STAR Protocols 2025
https://doi.org/10.1016/j.xpro.2025.103813
Embryonic dormancy (diapause) is a reproductive adaptation that allows some mammalian species to prolong pregnancy and delay birth by temporarily suspending embryonic development just before implantation. Here, we present a step-by-step protocol for inducing and maintaining embryonic diapause in mice by tamoxifen administration or ovariectomy. We describe steps for setting up mouse matings, the administration of pharmacological compounds, the surgical procedure for the removal of the ovaries, postoperative care, and the isolation of dormant embryos. We then describe procedures for triggering exit from diapause by administration of β-estradiol and the subsequent isolation of reactivated embryos.
Hou Y, Nie Z, Jiang Q, Velychko S, Heising S, Bedzhov I, Wu G, Adachi K, Scholer HR.
Elife 2025
https://doi.org/10.7554/elife.100735
During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.