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Your search keyword '"Popescu, Dorin-Mirel"' showing total 3 results
Start Over Author "Popescu, Dorin-Mirel" Topic single-cell analysis
3 results on '"Popescu, Dorin-Mirel"'

1. A prenatal skin atlas reveals immune regulation of human skin morphogenesis.

Author

Gopee NH, Winheim E, Olabi B, Admane C, Foster AR, Huang N, Botting RA, Torabi F, Sumanaweera D, Le AP, Kim J, Verger L, Stephenson E, Adão D, Ganier C, Gim KY, Serdy SA, Deakin C, Goh I, Steele L, Annusver K, Miah MU, Tun WM, Moghimi P, Kwakwa KA, Li T, Basurto Lozada D, Rumney B, Tudor CL, Roberts K, Chipampe NJ, Sidhpura K, Englebert J, Jardine L, Reynolds G, Rose A, Rowe V, Pritchard S, Mulas I, Fletcher J, Popescu DM, Poyner E, Dubois A, Guy A, Filby A, Lisgo S, Barker RA, Glass IA, Park JE, Vento-Tormo R, Nikolova MT, He P, Lawrence JEG, Moore J, Ballereau S, Hale CB, Shanmugiah V, Horsfall D, Rajan N, McGrath JA, O'Toole EA, Treutlein B, Bayraktar O, Kasper M, Progatzky F, Mazin P, Lee J, Gambardella L, Koehler KR, Teichmann SA, and Haniffa M

Subjects
Adult, Humans, Atlases as Topic, Endothelial Cells cytology, Endothelial Cells metabolism, Fetus cytology, Fetus embryology, Fetus immunology, Human Embryonic Stem Cells cytology, Human Embryonic Stem Cells metabolism, Immunity, Innate, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Macrophages immunology, Macrophages cytology, Macrophages metabolism, Multiomics, Neovascularization, Physiologic, Organoids cytology, Organoids embryology, Organoids metabolism, Skin Diseases genetics, Skin Diseases pathology, Transcriptome, Hair Follicle cytology, Hair Follicle embryology, Hair Follicle metabolism, Hair Follicle pathology, Morphogenesis, Single-Cell Analysis, Skin blood supply, Skin cytology, Skin embryology, Skin immunology, Skin metabolism, Skin pathology, Wound Healing genetics
Abstract

Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7-17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin 1 . The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells., Competing Interests: Competing interests: J.L. and K.R.K., with the Indiana University Research and Technology Corporation, have a patent relating to the methodology and composition of SkOs (PCT/US2016/058174). K.R.K. is a consultant for StemCell Technologies. All other authors declare no competing interests., (© 2024. The Author(s).)

Published
2024
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2. Decoding human fetal liver haematopoiesis

Author

Popescu, Dorin-Mirel, Botting, Rachel A, Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F, Polanski, Krzysztof, Goh, Issac, Efremova, Mirjana, Acres, Meghan, Maunder, Daniel, Vegh, Peter, Gitton, Yorick, Park, Jong-Eun, Vento-Tormo, Roser, Miao, Zhichao, Dixon, David, Rowell, Rachel, McDonald, David, Fletcher, James, Poyner, Elizabeth, Reynolds, Gary, Mather, Michael, Moldovan, Corina, Mamanova, Lira, Greig, Frankie, Young, Matthew D, Meyer, Kerstin B, Lisgo, Steven, Bacardit, Jaume, Fuller, Andrew, Millar, Ben, Innes, Barbara, Lindsay, Susan, Stubbington, Michael JT, Kowalczyk, Monika S, Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L, Slyper, Michal, Rozenblatt-Rosen, Orit, Filby, Andrew, Carey, Peter, Villani, Alexandra-Chloé, Roy, Anindita, Regev, Aviv, Chédotal, Alain, Roberts, Irene, Göttgens, Berthold, Behjati, Sam, Laurenti, Elisa, Teichmann, Sarah A, and Haniffa, Muzlifah

Subjects
Blood Cells, Lymphoid Tissue, Gene Expression Profiling, Stem Cells, Flow Cytometry, 3. Good health, Hematopoiesis, Fetus, Cellular Microenvironment, Liver, embryonic structures, Humans, Female, Single-Cell Analysis
Abstract

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs., We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC.

3. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors

Author

Young, Matthew D, Mitchell, Thomas J, Vieira Braga, Felipe A, Tran, Maxine GB, Stewart, Benjamin J, Ferdinand, John R, Collord, Grace, Botting, Rachel A, Popescu, Dorin-Mirel, Loudon, Kevin W, Vento-Tormo, Roser, Stephenson, Emily, Cagan, Alex, Farndon, Sarah J, Del Castillo Velasco-Herrera, Martin, Guzzo, Charlotte, Richoz, Nathan, Mamanova, Lira, Aho, Tevita, Armitage, James N, Riddick, Antony CP, Mushtaq, Imran, Farrell, Stephen, Rampling, Dyanne, Nicholson, James, Filby, Andrew, Burge, Johanna, Lisgo, Steven, Maxwell, Patrick H, Lindsay, Susan, Warren, Anne Y, Stewart, Grant D, Sebire, Neil, Coleman, Nicholas, Haniffa, Muzlifah, Teichmann, Sarah A, Clatworthy, Menna, and Behjati, Sam

Subjects
Adult, Genetic Variation, Humans, Single-Cell Analysis, Child, Kidney, Transcriptome, Carcinoma, Renal Cell, Wilms Tumor, Kidney Neoplasms, 3. Good health
Abstract

Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.

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