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  1. Article ; Online: Trained immunity and epigenetic memory in long-term self-renewing hematopoietic cells.

    Johansson, Alban / Lin, Dawn S / Mercier, Francois E / Yamashita, Masayuki / Divangahi, Maziar / Sieweke, Michael H

    Experimental hematology

    2023  Volume 121, Page(s) 6–11

    Abstract: Immunologic memory is a feature typically ascribed to the adaptive arm of the immune system. However, recent studies have demonstrated that hematopoietic stem cells (HSCs) and innate immune cells such as monocytes and macrophages can gain epigenetic ... ...

    Abstract Immunologic memory is a feature typically ascribed to the adaptive arm of the immune system. However, recent studies have demonstrated that hematopoietic stem cells (HSCs) and innate immune cells such as monocytes and macrophages can gain epigenetic signatures to enhance their response in the context of reinfection. This suggests the presence of long-term memory, a phenomenon referred to as trained immunity. Trained immunity in HSCs can occur via changes in the epigenetic landscape and enhanced chromatin accessibility in lineage-specific genes, as well as through metabolic alterations. These changes can lead to a skewing in lineage bias, particularly enhanced myelopoiesis and the generation of epigenetically modified innate immune cells that provide better protection against pathogens on secondary infection. Here, we summarize recent advancements in trained immunity and epigenetic memory formation in HSCs and self-renewing alveolar macrophages, which was the focus of the Spring 2022 International Society for Experimental Hematology (ISEH) webinar.
    MeSH term(s) Immunity, Innate/genetics ; Trained Immunity ; Epigenetic Memory ; Macrophages ; Immunologic Memory/genetics
    Language English
    Publishing date 2023-02-09
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2023.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Expanding hematopoietic stem cell ex vivo: recent advances and technical considerations.

    Rubio-Lara, Juan A / Igarashi, Kyomi J / Sood, Shubhankar / Johansson, Alban / Sommerkamp, Pia / Yamashita, Masayuki / Lin, Dawn S

    Experimental hematology

    2023  Volume 125-126, Page(s) 6–15

    Abstract: Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic hierarchy, which are responsible for sustaining the lifelong production of mature blood and immune cells. Due to their superior long-term regenerative capacity, HSC ... ...

    Abstract Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic hierarchy, which are responsible for sustaining the lifelong production of mature blood and immune cells. Due to their superior long-term regenerative capacity, HSC therapies such as stem cell transplantation have been used in a broad range of hematologic disorders. However, the rarity of this population in vivo considerably limits its clinical applications and large-scale analyses such as screening and safety studies. Therefore, ex vivo culture methods that allow long-term expansion and maintenance of functional HSCs are instrumental in overcoming the difficulties in studying HSC biology and improving HSC therapies. In this perspective, we discuss recent advances and technical considerations for three ex vivo HSC expansion methods including 1) polyvinyl alcohol-based HSC expansion, 2) mesenchymal stromal cell-HSC co-culture, and 3) two-/three-dimensional hydrogel HSC culture. This review summarizes the presentations and discussions from the 2022 International Society for Experimental Hematology (ISEH) Annual Meeting New Investigator Technology Session.
    MeSH term(s) Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Coculture Techniques ; Mesenchymal Stem Cells ; Cell Differentiation
    Language English
    Publishing date 2023-08-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2023.07.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immuno-Modulation of Hematopoietic Stem and Progenitor Cells in Inflammation.

    Sezaki, Maiko / Hayashi, Yoshikazu / Wang, Yuxin / Johansson, Alban / Umemoto, Terumasa / Takizawa, Hitoshi

    Frontiers in immunology

    2020  Volume 11, Page(s) 585367

    Abstract: Lifelong blood production is maintained by bone marrow (BM)-residing hematopoietic stem cells (HSCs) that are defined by two special properties: multipotency and self-renewal. Since dysregulation of either may lead to a differentiation block or extensive ...

    Abstract Lifelong blood production is maintained by bone marrow (BM)-residing hematopoietic stem cells (HSCs) that are defined by two special properties: multipotency and self-renewal. Since dysregulation of either may lead to a differentiation block or extensive proliferation causing dysplasia or neoplasia, the genomic integrity and cellular function of HSCs must be tightly controlled and preserved by cell-intrinsic programs and cell-extrinsic environmental factors of the BM. The BM had been long regarded an immune-privileged organ shielded from immune insults and inflammation, and was thereby assumed to provide HSCs and immune cells with a protective environment to ensure blood and immune homeostasis. Recently, accumulating evidence suggests that hemato-immune challenges such as autoimmunity, inflammation or infection elicit a broad spectrum of immunological reactions in the BM, and in turn, influence the function of HSCs and BM environmental cells. Moreover, in analogy with the emerging concept of "trained immunity", certain infection-associated stimuli are able to train HSCs and progenitors to produce mature immune cells with enhanced responsiveness to subsequent challenges, and in some cases, form an inflammatory or infectious memory in HSCs themselves. In this review, we will introduce recent findings on HSC and hematopoietic regulation upon exposure to various hemato-immune stimuli and discuss how these challenges can elicit either beneficial or detrimental outcomes on HSCs and the hemato-immune system, as well as their relevance to aging and hematologic malignancies.
    MeSH term(s) Aging/immunology ; Aging/pathology ; Animals ; Bone Marrow/immunology ; Cellular Microenvironment/immunology ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/pathology ; Hematopoietic Stem Cells/immunology ; Humans ; Immunologic Memory/immunology ; Inflammation/immunology
    Language English
    Publishing date 2020-11-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.585367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Direct lineage reprogramming of adult mouse fibroblast to erythroid progenitors

    Ilsley, Melissa / Capellera-Garcia, Sandra / Dhulipala, Kishori / Johansson, Alban / Flygare, Johan

    Journal of visualized experiments. 2018 Dec. 14, , no. 142

    2018  

    Abstract: Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of cell fate determining and maturing factors. We previously set out to define the minimal set of factors ... ...

    Abstract Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of cell fate determining and maturing factors. We previously set out to define the minimal set of factors necessary for instructing red blood cell development using direct lineage reprogramming of fibroblasts into induced erythroid progenitors/precursors (iEPs). We showed that overexpression of Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs that resemble bona fide erythroid cells in terms of morphology, phenotype, and gene expression. We intend that iEPs will provide an invaluable tool to study erythropoiesis and cell fate regulation. Here we describe the stepwise process of converting murine tail tip fibroblasts into iEPs via transcription factor-driven direct lineage reprogramming (DLR). In this example, we perform the reprogramming in fibroblasts from erythroid lineage-tracing mice that express the yellow fluorescent protein (YFP) under the control of the erythropoietin receptor gene (EpoR) promoter, enabling visualization of erythroid cell fate induction upon reprogramming. Following this protocol, fibroblasts can be reprogrammed into iEPs within five to eight days. While improvements can still be made to the process, we show that GTLM-mediated reprogramming is a rapid and direct process, yielding cells with properties of bona fide erythroid progenitor and precursor cells.
    Keywords GATA transcription factors ; adults ; erythrocytes ; erythropoiesis ; erythropoietin ; fibroblasts ; gene overexpression ; genes ; humans ; mice ; phenotype ; tail ; yellow fluorescent protein
    Language English
    Dates of publication 2018-1214
    Size p. e58464.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ISSN 1940-087X
    DOI 10.3791/58464
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: ATP citrate lyase controls hematopoietic stem cell fate and supports bone marrow regeneration.

    Umemoto, Terumasa / Johansson, Alban / Ahmad, Shah Adil Ishtiyaq / Hashimoto, Michihiro / Kubota, Sho / Kikuchi, Kenta / Odaka, Haruki / Era, Takumi / Kurotaki, Daisuke / Sashida, Goro / Suda, Toshio

    The EMBO journal

    2022  Volume 41, Issue 8, Page(s) e109463

    Abstract: In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic ... ...

    Abstract In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCR
    MeSH term(s) ATP Citrate (pro-S)-Lyase/genetics ; ATP Citrate (pro-S)-Lyase/metabolism ; Bone Marrow ; Endothelial Protein C Receptor/metabolism ; Hematopoietic Stem Cells/physiology ; Histones/metabolism
    Chemical Substances Endothelial Protein C Receptor ; Histones ; ATP Citrate (pro-S)-Lyase (EC 2.3.3.8)
    Language English
    Publishing date 2022-03-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2021109463
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Direct Lineage Reprogramming of Adult Mouse Fibroblast to Erythroid Progenitors.

    Ilsley, Melissa / Capellera-Garcia, Sandra / Dhulipala, Kishori / Johansson, Alban / Flygare, Johan

    Journal of visualized experiments : JoVE

    2018  , Issue 142

    Abstract: Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of cell fate determining and maturing factors. We previously set out to define the minimal set of factors ... ...

    Abstract Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of cell fate determining and maturing factors. We previously set out to define the minimal set of factors necessary for instructing red blood cell development using direct lineage reprogramming of fibroblasts into induced erythroid progenitors/precursors (iEPs). We showed that overexpression of Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs that resemble bona fide erythroid cells in terms of morphology, phenotype, and gene expression. We intend that iEPs will provide an invaluable tool to study erythropoiesis and cell fate regulation. Here we describe the stepwise process of converting murine tail tip fibroblasts into iEPs via transcription factor-driven direct lineage reprogramming (DLR). In this example, we perform the reprogramming in fibroblasts from erythroid lineage-tracing mice that express the yellow fluorescent protein (YFP) under the control of the erythropoietin receptor gene (EpoR) promoter, enabling visualization of erythroid cell fate induction upon reprogramming. Following this protocol, fibroblasts can be reprogrammed into iEPs within five to eight days. While improvements can still be made to the process, we show that GTLM-mediated reprogramming is a rapid and direct process, yielding cells with properties of bona fide erythroid progenitor and precursor cells.
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Cell Lineage ; Erythroid Precursor Cells/physiology ; Erythropoiesis/genetics ; Erythropoiesis/physiology ; Fibroblasts/physiology ; Gene Expression Regulation ; Gene Regulatory Networks ; Genetic Engineering ; Humans ; Mice ; Promoter Regions, Genetic ; Receptors, Erythropoietin/genetics ; Receptors, Erythropoietin/metabolism ; Transcription Factors/genetics
    Chemical Substances Receptors, Erythropoietin ; Transcription Factors
    Language English
    Publishing date 2018-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ISSN 1940-087X
    ISSN (online) 1940-087X
    DOI 10.3791/58464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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