Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells
Somatic mutation of ten-eleven translocation 2 ( TET2 ) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of Tet2 led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transforma...
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| Veröffentlicht in: | Scientific reports 2012-02, Vol.2 (1), p.273-273, Article 273 |
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| creator | Kunimoto, Hiroyoshi Fukuchi, Yumi Sakurai, Masatoshi Sadahira, Ken Ikeda, Yasuo Okamoto, Shinichiro Nakajima, Hideaki |
| description | Somatic mutation of ten-eleven translocation 2 (
TET2
) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of
Tet2
led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of
Tet2
loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of
Tet2
results in the expansion of Lin
−
Sca-1
+
c-Kit
+
(LSK) cells in FL. Furthermore,
Tet2
loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in
in vivo
serial transplantation assay. Disruption of
Tet2
in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli
in vitro
. These results demonstrate that
Tet2
plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL. |
| doi_str_mv | 10.1038/srep00273 |
| format | Article |
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TET2
) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of
Tet2
led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of
Tet2
loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of
Tet2
results in the expansion of Lin
−
Sca-1
+
c-Kit
+
(LSK) cells in FL. Furthermore,
Tet2
loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in
in vivo
serial transplantation assay. Disruption of
Tet2
in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli
in vitro
. These results demonstrate that
Tet2
plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep00273</identifier><identifier>PMID: 22355785</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/142 ; 631/337/176 ; 631/532 ; 692/308 ; Ablation ; Animals ; Blood cells ; Bone marrow ; Brain cancer ; c-Kit protein ; Cell Differentiation - genetics ; Cell self-renewal ; Competition ; Competitive advantage ; DNA-Binding Proteins - genetics ; Epigenetics ; Fetuses ; Flow Cytometry ; Genetic transformation ; Genomes ; Hematopoietic Stem Cells - cytology ; Hepatocytes ; Homeostasis ; Humanities and Social Sciences ; Leukemia ; Liver ; Liver - cytology ; Liver - embryology ; Mice ; Mice, Inbred C57BL ; multidisciplinary ; Mutation ; Proto-Oncogene Proteins - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Science ; Stem cells ; Translocation ; Transplantation ; Transplants & implants</subject><ispartof>Scientific reports, 2012-02, Vol.2 (1), p.273-273, Article 273</ispartof><rights>The Author(s) 2012</rights><rights>Copyright Nature Publishing Group Feb 2012</rights><rights>Copyright © 2012, Macmillan Publishers Limited. All rights reserved 2012 Macmillan Publishers Limited. All rights reserved</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-25b9c2e22d3d093dc7909948dd20678f038936bf683877e71cb1ec6426c981bd3</citedby><cites>FETCH-LOGICAL-c503t-25b9c2e22d3d093dc7909948dd20678f038936bf683877e71cb1ec6426c981bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281275/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281275/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22355785$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kunimoto, Hiroyoshi</creatorcontrib><creatorcontrib>Fukuchi, Yumi</creatorcontrib><creatorcontrib>Sakurai, Masatoshi</creatorcontrib><creatorcontrib>Sadahira, Ken</creatorcontrib><creatorcontrib>Ikeda, Yasuo</creatorcontrib><creatorcontrib>Okamoto, Shinichiro</creatorcontrib><creatorcontrib>Nakajima, Hideaki</creatorcontrib><title>Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Somatic mutation of ten-eleven translocation 2 (
TET2
) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of
Tet2
led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of
Tet2
loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of
Tet2
results in the expansion of Lin
−
Sca-1
+
c-Kit
+
(LSK) cells in FL. Furthermore,
Tet2
loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in
in vivo
serial transplantation assay. Disruption of
Tet2
in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli
in vitro
. These results demonstrate that
Tet2
plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL.</description><subject>631/136/142</subject><subject>631/337/176</subject><subject>631/532</subject><subject>692/308</subject><subject>Ablation</subject><subject>Animals</subject><subject>Blood cells</subject><subject>Bone marrow</subject><subject>Brain cancer</subject><subject>c-Kit protein</subject><subject>Cell Differentiation - genetics</subject><subject>Cell self-renewal</subject><subject>Competition</subject><subject>Competitive advantage</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epigenetics</subject><subject>Fetuses</subject><subject>Flow Cytometry</subject><subject>Genetic transformation</subject><subject>Genomes</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hepatocytes</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Leukemia</subject><subject>Liver</subject><subject>Liver - cytology</subject><subject>Liver - embryology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Science</subject><subject>Stem cells</subject><subject>Translocation</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkU9rFTEUxQdRbGm78AtIwIUoTE1u3kySjSCl_oGCm7oOmeROX8pMMiaZFr-9aV99PDWbXLi_nJzDaZpXjJ4zyuWHnHChFAR_1hwD3XQtcIDnB_NRc5bzLa2nA7Vh6mVzBMC7TsjuuEnXWIA4n9O6FB8DmdC4TEokGLYmWHQk4zS2CQPem4mY4IiZCqa6cH4c6xCKN49P40hGLBWa_B0mssXZlLhEj8VbkgvOxOI05dPmxWimjGdP90nz4_Pl9cXX9ur7l28Xn65a21FeWugGZQEBHHdUcWeFokptpHNAeyHHml3xfhh7yaUQKJgdGNp-A71Vkg2OnzQfd7rLOszobDWazKSX5GeTfulovP57E_xW38Q7zUEyEF0VePskkOLPFXPRs88PEUzAuGatgDMFHZOVfPMPeRvXFGo6zaQSXIlaRqXe7SibYq61jXsvjOqHLvW-y8q-PjS_J_80V4H3OyDXVbjBdPDlf2q_AXkWqdE</recordid><startdate>20120217</startdate><enddate>20120217</enddate><creator>Kunimoto, Hiroyoshi</creator><creator>Fukuchi, Yumi</creator><creator>Sakurai, Masatoshi</creator><creator>Sadahira, Ken</creator><creator>Ikeda, Yasuo</creator><creator>Okamoto, Shinichiro</creator><creator>Nakajima, Hideaki</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120217</creationdate><title>Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells</title><author>Kunimoto, Hiroyoshi ; Fukuchi, Yumi ; Sakurai, Masatoshi ; Sadahira, Ken ; Ikeda, Yasuo ; Okamoto, Shinichiro ; Nakajima, Hideaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-25b9c2e22d3d093dc7909948dd20678f038936bf683877e71cb1ec6426c981bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/136/142</topic><topic>631/337/176</topic><topic>631/532</topic><topic>692/308</topic><topic>Ablation</topic><topic>Animals</topic><topic>Blood cells</topic><topic>Bone marrow</topic><topic>Brain cancer</topic><topic>c-Kit protein</topic><topic>Cell Differentiation - genetics</topic><topic>Cell self-renewal</topic><topic>Competition</topic><topic>Competitive advantage</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epigenetics</topic><topic>Fetuses</topic><topic>Flow Cytometry</topic><topic>Genetic transformation</topic><topic>Genomes</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hepatocytes</topic><topic>Homeostasis</topic><topic>Humanities and Social Sciences</topic><topic>Leukemia</topic><topic>Liver</topic><topic>Liver - cytology</topic><topic>Liver - embryology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Science</topic><topic>Stem cells</topic><topic>Translocation</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kunimoto, Hiroyoshi</creatorcontrib><creatorcontrib>Fukuchi, Yumi</creatorcontrib><creatorcontrib>Sakurai, Masatoshi</creatorcontrib><creatorcontrib>Sadahira, Ken</creatorcontrib><creatorcontrib>Ikeda, Yasuo</creatorcontrib><creatorcontrib>Okamoto, Shinichiro</creatorcontrib><creatorcontrib>Nakajima, Hideaki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kunimoto, Hiroyoshi</au><au>Fukuchi, Yumi</au><au>Sakurai, Masatoshi</au><au>Sadahira, Ken</au><au>Ikeda, Yasuo</au><au>Okamoto, Shinichiro</au><au>Nakajima, Hideaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2012-02-17</date><risdate>2012</risdate><volume>2</volume><issue>1</issue><spage>273</spage><epage>273</epage><pages>273-273</pages><artnum>273</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Somatic mutation of ten-eleven translocation 2 (
TET2
) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of
Tet2
led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of
Tet2
loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of
Tet2
results in the expansion of Lin
−
Sca-1
+
c-Kit
+
(LSK) cells in FL. Furthermore,
Tet2
loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in
in vivo
serial transplantation assay. Disruption of
Tet2
in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli
in vitro
. These results demonstrate that
Tet2
plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22355785</pmid><doi>10.1038/srep00273</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/136/142 631/337/176 631/532 692/308 Ablation Animals Blood cells Bone marrow Brain cancer c-Kit protein Cell Differentiation - genetics Cell self-renewal Competition Competitive advantage DNA-Binding Proteins - genetics Epigenetics Fetuses Flow Cytometry Genetic transformation Genomes Hematopoietic Stem Cells - cytology Hepatocytes Homeostasis Humanities and Social Sciences Leukemia Liver Liver - cytology Liver - embryology Mice Mice, Inbred C57BL multidisciplinary Mutation Proto-Oncogene Proteins - genetics Reverse Transcriptase Polymerase Chain Reaction Science Stem cells Translocation Transplantation Transplants & implants |
| title | Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells |
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