SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment
The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial action of proteins that determine their self-renewal and/or their commitment to differentiation. Stem cell leukemia/T-cell acute lymphoblastic leukemia 1 (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor,...
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| Veröffentlicht in: | Blood 2005-10, Vol.106 (7), p.2318-2328 |
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| creator | Reynaud, Damien Ravet, Emmanuel Titeux, Monique Mazurier, Frédéric Rénia, Laurent Dubart-Kupperschmitt, Anne Roméo, Paul-Henri Pflumio, Françoise |
| description | The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial action of proteins that determine their self-renewal and/or their commitment to differentiation. Stem cell leukemia/T-cell acute lymphoblastic leukemia 1 (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor, plays key roles in controlling the development of primitive and definitive hematopoiesis during mouse development but its function in adult HSCs is still a matter of debate. We report here that the lentiviral-mediated enforced expression of TAL1 in human CD34+ cells marginally affects in vitro the differentiation of committed progenitors, whereas in vivo the repopulation capacity of the long-term SCID (severe combined immunodeficient) mouse–repopulating cells (LT-SRCs) is enhanced. As a consequence, the production of SRC-derived multipotent progenitors as well as erythroid- and myeloid-differentiated cells is increased. Looking at the lymphoid compartment, constitutive TAL1-enforced expression impairs B- but not T-cell differentiation. Expression of a mutant TAL1 protein that cannot bind DNA specifically impairs human LT-SRC amplification, indicating a DNA-binding dependent effect of TAL1 on primitive cell populations. These results indicate that TAL1 expression level regulates immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity. |
| doi_str_mv | 10.1182/blood-2005-02-0557 |
| format | Article |
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Stem cell leukemia/T-cell acute lymphoblastic leukemia 1 (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor, plays key roles in controlling the development of primitive and definitive hematopoiesis during mouse development but its function in adult HSCs is still a matter of debate. We report here that the lentiviral-mediated enforced expression of TAL1 in human CD34+ cells marginally affects in vitro the differentiation of committed progenitors, whereas in vivo the repopulation capacity of the long-term SCID (severe combined immunodeficient) mouse–repopulating cells (LT-SRCs) is enhanced. As a consequence, the production of SRC-derived multipotent progenitors as well as erythroid- and myeloid-differentiated cells is increased. Looking at the lymphoid compartment, constitutive TAL1-enforced expression impairs B- but not T-cell differentiation. Expression of a mutant TAL1 protein that cannot bind DNA specifically impairs human LT-SRC amplification, indicating a DNA-binding dependent effect of TAL1 on primitive cell populations. These results indicate that TAL1 expression level regulates immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2005-02-0557</identifier><identifier>PMID: 15961517</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Animals ; Antigens, CD19 - biosynthesis ; Antigens, CD34 - biosynthesis ; B-Lymphocytes - cytology ; Biological and medical sciences ; Blotting, Western ; Bone Marrow Cells - cytology ; Cell Differentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cells, Cultured ; DNA - metabolism ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Genetic Vectors ; Green Fluorescent Proteins - metabolism ; Hematopoiesis ; Hematopoietic Stem Cells - cytology ; Humans ; Intracellular Signaling Peptides and Proteins ; Lentivirus - metabolism ; Lewis X Antigen - biosynthesis ; Lipopolysaccharide Receptors - biosynthesis ; Mice ; Mice, SCID ; Models, Genetic ; Molecular and cellular biology ; Mutation ; Oncogene Proteins, Fusion ; Protein Binding ; T-Lymphocytes - cytology</subject><ispartof>Blood, 2005-10, Vol.106 (7), p.2318-2328</ispartof><rights>2005 American Society of Hematology</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-327dd7bd5c00b3050734b00d4d4d59bc1ac4ae7d734c49c2682c595be9d6ca653</citedby><cites>FETCH-LOGICAL-c428t-327dd7bd5c00b3050734b00d4d4d59bc1ac4ae7d734c49c2682c595be9d6ca653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17183703$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15961517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reynaud, Damien</creatorcontrib><creatorcontrib>Ravet, Emmanuel</creatorcontrib><creatorcontrib>Titeux, Monique</creatorcontrib><creatorcontrib>Mazurier, Frédéric</creatorcontrib><creatorcontrib>Rénia, Laurent</creatorcontrib><creatorcontrib>Dubart-Kupperschmitt, Anne</creatorcontrib><creatorcontrib>Roméo, Paul-Henri</creatorcontrib><creatorcontrib>Pflumio, Françoise</creatorcontrib><title>SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment</title><title>Blood</title><addtitle>Blood</addtitle><description>The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial action of proteins that determine their self-renewal and/or their commitment to differentiation. Stem cell leukemia/T-cell acute lymphoblastic leukemia 1 (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor, plays key roles in controlling the development of primitive and definitive hematopoiesis during mouse development but its function in adult HSCs is still a matter of debate. We report here that the lentiviral-mediated enforced expression of TAL1 in human CD34+ cells marginally affects in vitro the differentiation of committed progenitors, whereas in vivo the repopulation capacity of the long-term SCID (severe combined immunodeficient) mouse–repopulating cells (LT-SRCs) is enhanced. As a consequence, the production of SRC-derived multipotent progenitors as well as erythroid- and myeloid-differentiated cells is increased. Looking at the lymphoid compartment, constitutive TAL1-enforced expression impairs B- but not T-cell differentiation. Expression of a mutant TAL1 protein that cannot bind DNA specifically impairs human LT-SRC amplification, indicating a DNA-binding dependent effect of TAL1 on primitive cell populations. These results indicate that TAL1 expression level regulates immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity.</description><subject>Animals</subject><subject>Antigens, CD19 - biosynthesis</subject><subject>Antigens, CD34 - biosynthesis</subject><subject>B-Lymphocytes - cytology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Bone Marrow Cells - cytology</subject><subject>Cell Differentiation</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>DNA - metabolism</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Genetic Vectors</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Hematopoiesis</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Lentivirus - metabolism</subject><subject>Lewis X Antigen - biosynthesis</subject><subject>Lipopolysaccharide Receptors - biosynthesis</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Models, Genetic</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>Oncogene Proteins, Fusion</subject><subject>Protein Binding</subject><subject>T-Lymphocytes - cytology</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpabZp_0APRZf2pmYkW5YNvYSlX7CQQ9NrhSyNExVZ2kpykv77ersLuYU5DAzP-zI8hLzl8JHzXlyMISXHBIBkIBhIqZ6RDZeiZwACnpMNAHSsHRQ_I69K-Q3A20bIl-SMy6HjkqsN-fVju7u4vtxxig_7jKX4FGnAOww0480STMVCb5fZRHqLs6lpnzxWb2mpOFOLIdCCYWIZI96bQE10FONNNlOdMdbX5MVkQsE3p31Ofn75fL39xnZXX79vL3fMtqKvrBHKOTU6aQHGBiSoph0BXLuOHEbLjW0NKreebTtY0fXCykGOOLjOmk425-TDsXef058FS9WzL4fvTMS0FN31clB9J1ZQHEGbUykZJ73Pfjb5r-agD1b1f6v6YFWD0Aera-jdqX0ZZ3SPkZPGFXh_AkyxJkzZROvLI6d43yhoVu7TkcPVxZ3HrIv1GC06n9FW7ZJ_6o9_TdyV5w</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Reynaud, Damien</creator><creator>Ravet, Emmanuel</creator><creator>Titeux, Monique</creator><creator>Mazurier, Frédéric</creator><creator>Rénia, Laurent</creator><creator>Dubart-Kupperschmitt, Anne</creator><creator>Roméo, Paul-Henri</creator><creator>Pflumio, Françoise</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20051001</creationdate><title>SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment</title><author>Reynaud, Damien ; Ravet, Emmanuel ; Titeux, Monique ; Mazurier, Frédéric ; Rénia, Laurent ; Dubart-Kupperschmitt, Anne ; Roméo, Paul-Henri ; Pflumio, Françoise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-327dd7bd5c00b3050734b00d4d4d59bc1ac4ae7d734c49c2682c595be9d6ca653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antigens, CD19 - biosynthesis</topic><topic>Antigens, CD34 - biosynthesis</topic><topic>B-Lymphocytes - cytology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Bone Marrow Cells - cytology</topic><topic>Cell Differentiation</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cells, Cultured</topic><topic>DNA - metabolism</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation</topic><topic>Genetic Vectors</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Hematopoiesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Lentivirus - metabolism</topic><topic>Lewis X Antigen - biosynthesis</topic><topic>Lipopolysaccharide Receptors - biosynthesis</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Models, Genetic</topic><topic>Molecular and cellular biology</topic><topic>Mutation</topic><topic>Oncogene Proteins, Fusion</topic><topic>Protein Binding</topic><topic>T-Lymphocytes - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reynaud, Damien</creatorcontrib><creatorcontrib>Ravet, Emmanuel</creatorcontrib><creatorcontrib>Titeux, Monique</creatorcontrib><creatorcontrib>Mazurier, Frédéric</creatorcontrib><creatorcontrib>Rénia, Laurent</creatorcontrib><creatorcontrib>Dubart-Kupperschmitt, Anne</creatorcontrib><creatorcontrib>Roméo, Paul-Henri</creatorcontrib><creatorcontrib>Pflumio, Françoise</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reynaud, Damien</au><au>Ravet, Emmanuel</au><au>Titeux, Monique</au><au>Mazurier, Frédéric</au><au>Rénia, Laurent</au><au>Dubart-Kupperschmitt, Anne</au><au>Roméo, Paul-Henri</au><au>Pflumio, Françoise</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>106</volume><issue>7</issue><spage>2318</spage><epage>2328</epage><pages>2318-2328</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial action of proteins that determine their self-renewal and/or their commitment to differentiation. 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Expression of a mutant TAL1 protein that cannot bind DNA specifically impairs human LT-SRC amplification, indicating a DNA-binding dependent effect of TAL1 on primitive cell populations. These results indicate that TAL1 expression level regulates immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>15961517</pmid><doi>10.1182/blood-2005-02-0557</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, CD19 - biosynthesis Antigens, CD34 - biosynthesis B-Lymphocytes - cytology Biological and medical sciences Blotting, Western Bone Marrow Cells - cytology Cell Differentiation Cell differentiation, maturation, development, hematopoiesis Cell physiology Cells, Cultured DNA - metabolism Flow Cytometry Fundamental and applied biological sciences. Psychology Gene Expression Regulation Genetic Vectors Green Fluorescent Proteins - metabolism Hematopoiesis Hematopoietic Stem Cells - cytology Humans Intracellular Signaling Peptides and Proteins Lentivirus - metabolism Lewis X Antigen - biosynthesis Lipopolysaccharide Receptors - biosynthesis Mice Mice, SCID Models, Genetic Molecular and cellular biology Mutation Oncogene Proteins, Fusion Protein Binding T-Lymphocytes - cytology |
| title | SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment |
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