26 results found
Luis TC, 2021, Unwinding the role of Chd8 helicase in hematopoiesis, BLOOD, Vol: 138, Pages: 206-207, ISSN: 0006-4971
Haltalli MLR, Watcham S, Wilson NK, et al., 2020, Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection, Nature Cell Biology, Vol: 22, Pages: 1399-1410, ISSN: 1465-7392
Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single-cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over substantially faster than at steady-state and HSC function is drastically affected. Interferon is found to affect both haematopoietic and mesenchymal BM cells and we specifically identify a dramatic loss of osteoblasts and alterations in endothelial cell function. Osteo-active parathyroid hormone treatment abolishes infection-triggered HSC proliferation and—coupled with reactive oxygen species quenching—enables partial rescuing of HSC function.
Carrelha J, Lin DS, Rodriguez-Fraticelli AE, et al., 2020, Single-cell lineage tracing approaches in hematology research: technical considerations, EXPERIMENTAL HEMATOLOGY, Vol: 89, Pages: 26-36, ISSN: 0301-472X
Luis TC, Lawson H, Kranc KR, 2020, Divide and Rule: Mitochondrial Fission Regulates Quiescence in Hematopoietic Stem Cells, CELL STEM CELL, Vol: 26, Pages: 299-301, ISSN: 1934-5909
Duarte S, Woll PS, Buza-Vidas N, et al., 2018, Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis, BLOOD, Vol: 131, Pages: 1712-1719, ISSN: 0006-4971
Carrelha J, Meng Y, Kettyle LM, et al., 2018, Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells, NATURE, Vol: 554, Pages: 106-+, ISSN: 0028-0836
Breitbach M, Kimura K, Luis TC, et al., 2018, In vivo labeling by CD73 marks multipotent stromal cells and highlights endothelial heterogeneity in the bone marrow niche, Cell Stem Cell, Vol: 22, Pages: 262-+, ISSN: 1934-5909
Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP+ MSCs in various organs. In vivo, EGFP+ mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP+ cells exhibited a perivascular distribution pattern. EGFP+ cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential. Moreover, in the central bone marrow CD73-EGFP+ specifically labeled sinusoidal endothelial cells, thought to be a critical component of the hematopoietic stem cell niche. Purification and molecular characterization of this CD73-EGFP+ population revealed an endothelial subtype that also displays a mesenchymal signature, highlighting endothelial cell heterogeneity in the marrow. Thus, the CD73-EGFP mouse is a powerful tool for studying MSCs and sinusoidal endothelium.
Beerman I, Luis TC, Singbrant S, et al., 2017, The evolving view of the hematopoietic stem cell niche, Experimental Hematology, Vol: 50, Pages: 22-26, ISSN: 0301-472X
Hematopoietic stem cells (HSCs) reside in specialized microenvironments known as niches. The niche is essential to support HSC function and to maintain a correct balance between self-renewal and differentiation. Recent advances in defining different mesenchymal and endothelial bone marrow cell populations, as well as hematopoietic stem and progenitor cells, greatly enhanced our understanding of these niches and of the molecular mechanisms by which they regulate HSC function. In addition to the role in maintaining HSC homeostasis, the niche has also been implicated in the pathogenesis of blood disorders including hematological malignancies. Characterizing the extrinsic regulators and the cellular context in which the niches interact with HSCs will be crucial to define new strategies to enhance blood regeneration. Furthermore, a better understanding of the role of the niche in leukemia development will open new possibilities for the treatment of these disorders by using therapies aiming to target the leukemic niche specifically. To update on recent findings on this topic, the International Society for Experimental Hematology (ISEH) organized a webinar, presented by Prof. Sean J. Morrison and Dr. Simón Méndez-Ferrer and moderated by Dr. Cristina Lo Celso, entitled "The evolving view of the hematopoietic stem cell niche," which we summarize here.
Luis TC, Luc S, Mizukami T, et al., 2016, Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors, Nature Immunology, Vol: 17, Pages: 1424-1435, ISSN: 1529-2908
The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell–restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs.
Luis TC, Tremblay CS, Manz MG, et al., 2016, Inflammatory signals in HSPC development and homeostasis: Too much of a good thing?, EXPERIMENTAL HEMATOLOGY, Vol: 44, Pages: 908-912, ISSN: 0301-472X
Grover A, Sanjuan-Pla A, Thongjuea S, et al., 2016, Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723
Buono M, Facchini R, Matsuoka S, et al., 2016, A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors, NATURE CELL BIOLOGY, Vol: 18, Pages: 157-+, ISSN: 1465-7392
Boiers C, Carrelha J, Lutteropp M, et al., 2013, Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells, CELL STEM CELL, Vol: 13, Pages: 535-548, ISSN: 1934-5909
Sanjuan-Pla A, Macaulay IC, Jensen CT, et al., 2013, Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy, NATURE, Vol: 502, Pages: 232-+, ISSN: 0028-0836
Luc S, Luis TC, Boukarabila H, et al., 2012, The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential, NATURE IMMUNOLOGY, Vol: 13, Pages: 412-419, ISSN: 1529-2908
Luis TC, Ichii M, Brugman MH, et al., 2012, Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development, LEUKEMIA, Vol: 26, Pages: 414-421, ISSN: 0887-6924
Luis TC, Killmann NM-B, Staal FJT, 2012, Signal transduction pathways regulating hematopoietic stem cell biology: Introduction to a series of Spotlight Reviews, LEUKEMIA, Vol: 26, Pages: 86-90, ISSN: 0887-6924
Luis TC, Naber BAE, Roozen PPC, et al., 2011, Canonical Wnt Signaling Regulates Hematopoiesis in a Dosage-Dependent Fashion, CELL STEM CELL, Vol: 9, Pages: 345-356, ISSN: 1934-5909
Luis TC, Naber BAE, Fibbe WE, et al., 2010, Wnt3a nonredundantly controls hematopoietic stem cell function and its deficiency results in complete absence of canonical Wnt signaling, BLOOD, Vol: 116, Pages: 496-497, ISSN: 0006-4971
Staal FJT, Luis TC, 2010, Wnt Signaling in Hematopoiesis: Crucial Factors for Self-Renewal, Proliferation, and Cell fate Decisions, JOURNAL OF CELLULAR BIOCHEMISTRY, Vol: 109, Pages: 844-849, ISSN: 0730-2312
Luis TC, Weerkamp F, Naber BAE, et al., 2009, Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation, BLOOD, Vol: 113, Pages: 546-554, ISSN: 0006-4971
Luis TC, Staal FJT, 2009, WNT Proteins: Environmental Factors Regulating HSC Fate in the Niche, HEMATOPOIETIC STEM CELLS VII, Vol: 1176, Pages: 70-76, ISSN: 0077-8923
Staal FJT, Luis TC, Tiemessen MM, 2008, WNT signalling in the immune system: WNT is spreading its wings, NATURE REVIEWS IMMUNOLOGY, Vol: 8, Pages: 581-593, ISSN: 1474-1733
Ferreira NJ, de Sousa IGM, Luis TC, et al., 2007, Pittosporum undulatum Vent. grown in Portugal: secretory structures, seasonal variation and enantiomeric composition of its essential oil, FLAVOUR AND FRAGRANCE JOURNAL, Vol: 22, Pages: 1-9, ISSN: 0882-5734
Weerkamp F, Luis TC, Naber BAE, et al., 2006, Identification of Notch target genes in uncommitted T-cell progenitors: no direct induction of a T-cell specific gene program, LEUKEMIA, Vol: 20, Pages: 1967-1977, ISSN: 0887-6924
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