Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi
Hematopoietic stem cells (HSCs) are characterized by their dual abilities to undergo differentiation into multiple hematopoietic cell lineages or to undergo self-renewal. The molecular basis of these properties remains poorly understood. Recently the piwi gene was found in the embryonic germline ste...
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Veröffentlicht in: | Blood 2001-01, Vol.97 (2), p.426-434 |
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description | Hematopoietic stem cells (HSCs) are characterized by their dual abilities to undergo differentiation into multiple hematopoietic cell lineages or to undergo self-renewal. The molecular basis of these properties remains poorly understood. Recently the piwi gene was found in the embryonic germline stem cells (GSCs) of Drosophila melanogaster and has been shown to be important in GSC self-renewal. This study demonstrated that hiwi, a novel human homologue of piwi, is also present in human CD34(+) hematopoietic progenitor cells but not in more differentiated cell populations. Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period. Expression of the hiwi gene was detected in many developing fetal and adult tissues. By means of 5' RACE cloning methodology, a novel putative full-length hiwi complementary DNA was cloned from human CD34(+) marrow cells. At the amino acid level, the human HIWI protein was 52% homologous to the Drosophila protein. The transient expression of hiwi in the human leukemia cell line KG1 resulted in a dramatic reduction in cellular proliferation. Overexpression of hiwi led to programmed cell death of KG1 cells as demonstrated by the Annexin V assay system. These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells. |
doi_str_mv | 10.1182/blood.V97.2.426 |
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The molecular basis of these properties remains poorly understood. Recently the piwi gene was found in the embryonic germline stem cells (GSCs) of Drosophila melanogaster and has been shown to be important in GSC self-renewal. This study demonstrated that hiwi, a novel human homologue of piwi, is also present in human CD34(+) hematopoietic progenitor cells but not in more differentiated cell populations. Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period. Expression of the hiwi gene was detected in many developing fetal and adult tissues. By means of 5' RACE cloning methodology, a novel putative full-length hiwi complementary DNA was cloned from human CD34(+) marrow cells. At the amino acid level, the human HIWI protein was 52% homologous to the Drosophila protein. The transient expression of hiwi in the human leukemia cell line KG1 resulted in a dramatic reduction in cellular proliferation. Overexpression of hiwi led to programmed cell death of KG1 cells as demonstrated by the Annexin V assay system. These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V97.2.426</identifier><identifier>PMID: 11154219</identifier><language>eng</language><publisher>Washington, DC: The Americain Society of Hematology</publisher><subject>Animals ; Antigens, CD34 ; Apoptosis - drug effects ; Argonaute Proteins ; Biological and medical sciences ; Bone Marrow Cells - cytology ; Bone Marrow Cells - immunology ; Bone Marrow Cells - metabolism ; Cell Culture Techniques ; Cell Differentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell Division - drug effects ; Cell physiology ; Chromosome Mapping ; Chromosomes, Human, Pair 12 - genetics ; Cloning, Molecular ; DNA, Complementary ; Drosophila - chemistry ; Drosophila Proteins ; Formazans ; Fundamental and applied biological sciences. Psychology ; Humans ; Insect Proteins - chemistry ; Molecular and cellular biology ; Molecular Sequence Data ; Proteins - genetics ; Proteins - metabolism ; Proteins - pharmacology ; RNA-Induced Silencing Complex ; Sequence Alignment ; Sequence Homology, Amino Acid ; Stem Cells - cytology ; Stem Cells - immunology ; Stem Cells - metabolism ; Tetrazolium Salts ; Transfection ; Tumor Cells, Cultured</subject><ispartof>Blood, 2001-01, Vol.97 (2), p.426-434</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c281t-ef6bb0d2a442feffddf2563ba7b9ba594072e00ae75dc4283e46192ecb5d96063</citedby></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=942450$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11154219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SHARMA, Arun K</creatorcontrib><creatorcontrib>NELSON, Mary C</creatorcontrib><creatorcontrib>BRANDT, John E</creatorcontrib><creatorcontrib>WESSMAN, Maija</creatorcontrib><creatorcontrib>MAHMUD, Nadim</creatorcontrib><creatorcontrib>WELLER, Kevin P</creatorcontrib><creatorcontrib>HOFFMAN, Ronald</creatorcontrib><title>Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi</title><title>Blood</title><addtitle>Blood</addtitle><description>Hematopoietic stem cells (HSCs) are characterized by their dual abilities to undergo differentiation into multiple hematopoietic cell lineages or to undergo self-renewal. The molecular basis of these properties remains poorly understood. Recently the piwi gene was found in the embryonic germline stem cells (GSCs) of Drosophila melanogaster and has been shown to be important in GSC self-renewal. This study demonstrated that hiwi, a novel human homologue of piwi, is also present in human CD34(+) hematopoietic progenitor cells but not in more differentiated cell populations. Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period. Expression of the hiwi gene was detected in many developing fetal and adult tissues. By means of 5' RACE cloning methodology, a novel putative full-length hiwi complementary DNA was cloned from human CD34(+) marrow cells. At the amino acid level, the human HIWI protein was 52% homologous to the Drosophila protein. The transient expression of hiwi in the human leukemia cell line KG1 resulted in a dramatic reduction in cellular proliferation. Overexpression of hiwi led to programmed cell death of KG1 cells as demonstrated by the Annexin V assay system. These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells.</description><subject>Animals</subject><subject>Antigens, CD34</subject><subject>Apoptosis - drug effects</subject><subject>Argonaute Proteins</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - immunology</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cell Culture Techniques</subject><subject>Cell Differentiation</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Division - drug effects</subject><subject>Cell physiology</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 12 - genetics</subject><subject>Cloning, Molecular</subject><subject>DNA, Complementary</subject><subject>Drosophila - chemistry</subject><subject>Drosophila Proteins</subject><subject>Formazans</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Insect Proteins - chemistry</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Proteins - pharmacology</subject><subject>RNA-Induced Silencing Complex</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Amino Acid</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - immunology</subject><subject>Stem Cells - metabolism</subject><subject>Tetrazolium Salts</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9z71PwzAUBHALgWgpzGzIEiMkPL_YSTyiFihSJRZgYajs-LkJSuoobgX891TlY7rldycdY-cCUiFKvLFtCC591UWKqcT8gI2FwjIBQDhkYwDIE6kLMWInMb4DCJmhOmYjIYSSKPSYvc23nVnz6SyTVzxuqOMVtW3k9NkPFCPf1MTr5qPhK1rTNTe83vs6dKENqy3x4PdmNoQY-rppzV7yftc5ZUfetJHOfnPCXu7vnqfzZPH08Di9XSQVlmKTkM-tBYdGSvTkvXMeVZ5ZU1htjdISCiQAQ4VylcQyI5kLjVRZ5XQOeTZhFz-7_dZ25Jb90HRm-Fr-vdyBy19gYmVaP5h11cR_pyVKBdk3csRhDA</recordid><startdate>20010115</startdate><enddate>20010115</enddate><creator>SHARMA, Arun K</creator><creator>NELSON, Mary C</creator><creator>BRANDT, John E</creator><creator>WESSMAN, Maija</creator><creator>MAHMUD, Nadim</creator><creator>WELLER, Kevin P</creator><creator>HOFFMAN, Ronald</creator><general>The Americain Society of Hematology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20010115</creationdate><title>Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi</title><author>SHARMA, Arun K ; NELSON, Mary C ; BRANDT, John E ; WESSMAN, Maija ; MAHMUD, Nadim ; WELLER, Kevin P ; HOFFMAN, Ronald</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c281t-ef6bb0d2a442feffddf2563ba7b9ba594072e00ae75dc4283e46192ecb5d96063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antigens, CD34</topic><topic>Apoptosis - drug effects</topic><topic>Argonaute Proteins</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - immunology</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Cell Culture Techniques</topic><topic>Cell Differentiation</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Division - drug effects</topic><topic>Cell physiology</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 12 - genetics</topic><topic>Cloning, Molecular</topic><topic>DNA, Complementary</topic><topic>Drosophila - chemistry</topic><topic>Drosophila Proteins</topic><topic>Formazans</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Insect Proteins - chemistry</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Proteins - pharmacology</topic><topic>RNA-Induced Silencing Complex</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Amino Acid</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - immunology</topic><topic>Stem Cells - metabolism</topic><topic>Tetrazolium Salts</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHARMA, Arun K</creatorcontrib><creatorcontrib>NELSON, Mary C</creatorcontrib><creatorcontrib>BRANDT, John E</creatorcontrib><creatorcontrib>WESSMAN, Maija</creatorcontrib><creatorcontrib>MAHMUD, Nadim</creatorcontrib><creatorcontrib>WELLER, Kevin P</creatorcontrib><creatorcontrib>HOFFMAN, Ronald</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SHARMA, Arun K</au><au>NELSON, Mary C</au><au>BRANDT, John E</au><au>WESSMAN, Maija</au><au>MAHMUD, Nadim</au><au>WELLER, Kevin P</au><au>HOFFMAN, Ronald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2001-01-15</date><risdate>2001</risdate><volume>97</volume><issue>2</issue><spage>426</spage><epage>434</epage><pages>426-434</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Hematopoietic stem cells (HSCs) are characterized by their dual abilities to undergo differentiation into multiple hematopoietic cell lineages or to undergo self-renewal. The molecular basis of these properties remains poorly understood. Recently the piwi gene was found in the embryonic germline stem cells (GSCs) of Drosophila melanogaster and has been shown to be important in GSC self-renewal. This study demonstrated that hiwi, a novel human homologue of piwi, is also present in human CD34(+) hematopoietic progenitor cells but not in more differentiated cell populations. Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period. Expression of the hiwi gene was detected in many developing fetal and adult tissues. By means of 5' RACE cloning methodology, a novel putative full-length hiwi complementary DNA was cloned from human CD34(+) marrow cells. At the amino acid level, the human HIWI protein was 52% homologous to the Drosophila protein. The transient expression of hiwi in the human leukemia cell line KG1 resulted in a dramatic reduction in cellular proliferation. Overexpression of hiwi led to programmed cell death of KG1 cells as demonstrated by the Annexin V assay system. These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells.</abstract><cop>Washington, DC</cop><pub>The Americain Society of Hematology</pub><pmid>11154219</pmid><doi>10.1182/blood.V97.2.426</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Antigens, CD34 Apoptosis - drug effects Argonaute Proteins Biological and medical sciences Bone Marrow Cells - cytology Bone Marrow Cells - immunology Bone Marrow Cells - metabolism Cell Culture Techniques Cell Differentiation Cell differentiation, maturation, development, hematopoiesis Cell Division - drug effects Cell physiology Chromosome Mapping Chromosomes, Human, Pair 12 - genetics Cloning, Molecular DNA, Complementary Drosophila - chemistry Drosophila Proteins Formazans Fundamental and applied biological sciences. Psychology Humans Insect Proteins - chemistry Molecular and cellular biology Molecular Sequence Data Proteins - genetics Proteins - metabolism Proteins - pharmacology RNA-Induced Silencing Complex Sequence Alignment Sequence Homology, Amino Acid Stem Cells - cytology Stem Cells - immunology Stem Cells - metabolism Tetrazolium Salts Transfection Tumor Cells, Cultured |
title | Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi |
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