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  1. Article ; Online: Direct lineage reprogramming: a useful addition to the blood cell research toolbox.

    Capellera-Garcia, Sandra / Flygare, Johan

    Expert review of hematology

    2017  Volume 10, Issue 2, Page(s) 107–109

    MeSH term(s) Animals ; Biomedical Research ; Blood Cells ; Cellular Reprogramming ; Cellular Reprogramming Techniques ; Humans
    Language English
    Publishing date 2017-01-05
    Publishing country England
    Document type Editorial
    ZDB-ID 2516804-6
    ISSN 1747-4094 ; 1747-4086
    ISSN (online) 1747-4094
    ISSN 1747-4086
    DOI 10.1080/17474086.2017.1272409
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  2. 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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  3. Article ; Online: Mapping human haematopoietic stem cells from haemogenic endothelium to birth.

    Calvanese, Vincenzo / Capellera-Garcia, Sandra / Ma, Feiyang / Fares, Iman / Liebscher, Simone / Ng, Elizabeth S / Ekstrand, Sophia / Aguadé-Gorgorió, Júlia / Vavilina, Anastasia / Lefaudeux, Diane / Nadel, Brian / Li, Jacky Y / Wang, Yanling / Lee, Lydia K / Ardehali, Reza / Iruela-Arispe, M Luisa / Pellegrini, Matteo / Stanley, Ed G / Elefanty, Andrew G /
    Schenke-Layland, Katja / Mikkola, Hanna K A

    Nature

    2022  Volume 604, Issue 7906, Page(s) 534–540

    Abstract: The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic ... ...

    Abstract The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites
    MeSH term(s) Cell Differentiation ; Endothelial Cells ; Endothelium ; Female ; Hematopoiesis ; Hematopoietic Stem Cells ; Humans ; Mesonephros ; Pregnancy
    Language English
    Publishing date 2022-04-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04571-x
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    Zs.A 26: Show issues Location:
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    Zs.MO 244: Show issues

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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: Correction: S100A6 is a critical regulator of hematopoietic stem cells.

    Grahn, Tan Hooi Min / Niroula, Abhishek / Végvári, Ákos / Oburoglu, Leal / Pertesi, Maroulio / Warsi, Sarah / Safi, Fatemeh / Miharada, Natsumi / Capellera-Garcia, Sandra / Siva, Kavitha / Liu, Yang / Rörby, Emma / Nilsson, Björn / Zubarev, Roman A / Karlsson, Stefan

    Leukemia

    2020  Volume 34, Issue 12, Page(s) 3439

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Language English
    Publishing date 2020-07-07
    Publishing country England
    Document type Published Erratum
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-020-0971-1
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  6. Article ; Online: Direct Conversion of Fibroblasts to Megakaryocyte Progenitors.

    Pulecio, Julian / Alejo-Valle, Oriol / Capellera-Garcia, Sandra / Vitaloni, Marianna / Rio, Paula / Mejía-Ramírez, Eva / Caserta, Ilaria / Bueren, Juan A / Flygare, Johan / Raya, Angel

    Cell reports

    2016  Volume 17, Issue 3, Page(s) 671–683

    Abstract: Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic ... ...

    Abstract Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41
    Language English
    Publishing date 2016-10-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2016.09.036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion.

    Capellera-Garcia, Sandra / Pulecio, Julian / Dhulipala, Kishori / Siva, Kavitha / Rayon-Estrada, Violeta / Singbrant, Sofie / Sommarin, Mikael N E / Walkley, Carl R / Soneji, Shamit / Karlsson, Göran / Raya, Ángel / Sankaran, Vijay G / Flygare, Johan

    Cell reports

    2016  Volume 15, Issue 11, Page(s) 2550–2562

    Abstract: Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell ( ... ...

    Abstract Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.
    MeSH term(s) Aging ; Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Cellular Reprogramming/genetics ; Colony-Forming Units Assay ; Erythroblasts/cytology ; Erythroblasts/metabolism ; Erythropoiesis/genetics ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Globins/genetics ; Globins/metabolism ; Humans ; Mice, Inbred C57BL ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors ; Globins (9004-22-2)
    Language English
    Publishing date 2016--14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2016.05.027
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  8. Article ; Online: Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

    Julian Pulecio / Oriol Alejo-Valle / Sandra Capellera-Garcia / Marianna Vitaloni / Paula Rio / Eva Mejía-Ramírez / Ilaria Caserta / Juan A. Bueren / Johan Flygare / Angel Raya

    Cell Reports, Vol 17, Iss 3, Pp 671-

    2016  Volume 683

    Abstract: Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic ... ...

    Abstract Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41+, display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.
    Keywords transdifferentiation ; lineage conversion ; Fanconi anemia ; thrombocytopenia ; platelets ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2016-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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