Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis
A genomic variant in the human ADTRP [androgen‐dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that ad...
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| creator | Wang, Li Wang, Xiaojing Wang, Longfei Yousaf, Muhammad Li, Jia Zuo, Mengxia Yang, Zhongcheng Gou, Dongzhi Bao, Binghao Li, Lei Xiang, Ning Jia, Haibo Xu, Chengqi Chen, Qiuyun Wang, Qing Kenneth |
| description | A genomic variant in the human ADTRP [androgen‐dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vas‐ culogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrpl and adtrp2). Knockdown of adtrpl expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp, flila, and scl; blocks primitive hematopoiesis, as shown by decreased expression of pu.1, mpo, and l‐plastin; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c‐myb. However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h‐bae1) or vasculogenesis (no effect on kdrl, ephb2a, notch3, dab2, or flt4). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang L., Wang X., Wang L., Yousaf, M., Li, J., Zuo, M., Yang Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang Q. K. Identificationofanew adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis. FASEB J. 32, 183‐194 (2018). www.fasebj.org |
| doi_str_mv | 10.1096/fj.201700166RR |
| format | Article |
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TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vas‐ culogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrpl and adtrp2). Knockdown of adtrpl expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp, flila, and scl; blocks primitive hematopoiesis, as shown by decreased expression of pu.1, mpo, and l‐plastin; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c‐myb. However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h‐bae1) or vasculogenesis (no effect on kdrl, ephb2a, notch3, dab2, or flt4). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang L., Wang X., Wang L., Yousaf, M., Li, J., Zuo, M., Yang Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang Q. K. Identificationofanew adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis. FASEB J. 32, 183‐194 (2018). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.201700166RR</identifier><identifier>PMID: 28877957</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>aggf1 ; Animals ; Animals, Genetically Modified ; Biomarkers ; c-Myb protein ; Cardiovascular disease ; Cell Differentiation ; coagulation ; Coronary artery ; Coronary artery disease ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Erythropoiesis ; GATA-1 protein ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Health risks ; Heart diseases ; Hemangioblasts ; Hemangioblasts - cytology ; Hemangioblasts - metabolism ; Hematopoiesis ; Hematopoiesis - genetics ; Hematopoietic stem cells ; Humans ; Inhibitors ; Lipoproteins - antagonists & inhibitors ; Lipoproteins - genetics ; Lipoproteins - metabolism ; Myelopoiesis ; Myelopoiesis - genetics ; Neovascularization, Physiologic - genetics ; PU.1 protein ; Runx1 protein ; Specifications ; Stem cells ; Tissue factor ; vascular development ; Zebrafish ; Zebrafish - embryology ; Zebrafish - genetics ; Zebrafish - metabolism ; Zebrafish Proteins - antagonists & inhibitors ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>The FASEB journal, 2018-01, Vol.32 (1), p.183-194</ispartof><rights>FASEB</rights><rights>FASEB.</rights><rights>Copyright Federation of American Societies for Experimental Biology (FASEB) Jan 2018</rights><rights>FASEB 2018 FASEB</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472R-dcf0c6b51999e924076549630f6312f9469c233617077f346580cd742c87bab43</citedby><cites>FETCH-LOGICAL-c472R-dcf0c6b51999e924076549630f6312f9469c233617077f346580cd742c87bab43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.201700166RR$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.201700166RR$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28877957$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Wang, Longfei</creatorcontrib><creatorcontrib>Yousaf, Muhammad</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Zuo, Mengxia</creatorcontrib><creatorcontrib>Yang, Zhongcheng</creatorcontrib><creatorcontrib>Gou, Dongzhi</creatorcontrib><creatorcontrib>Bao, Binghao</creatorcontrib><creatorcontrib>Li, Lei</creatorcontrib><creatorcontrib>Xiang, Ning</creatorcontrib><creatorcontrib>Jia, Haibo</creatorcontrib><creatorcontrib>Xu, Chengqi</creatorcontrib><creatorcontrib>Chen, Qiuyun</creatorcontrib><creatorcontrib>Wang, Qing Kenneth</creatorcontrib><title>Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>A genomic variant in the human ADTRP [androgen‐dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vas‐ culogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrpl and adtrp2). Knockdown of adtrpl expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp, flila, and scl; blocks primitive hematopoiesis, as shown by decreased expression of pu.1, mpo, and l‐plastin; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c‐myb. However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h‐bae1) or vasculogenesis (no effect on kdrl, ephb2a, notch3, dab2, or flt4). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang L., Wang X., Wang L., Yousaf, M., Li, J., Zuo, M., Yang Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang Q. K. Identificationofanew adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis. FASEB J. 32, 183‐194 (2018). www.fasebj.org</description><subject>aggf1</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Biomarkers</subject><subject>c-Myb protein</subject><subject>Cardiovascular disease</subject><subject>Cell Differentiation</subject><subject>coagulation</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Erythropoiesis</subject><subject>GATA-1 protein</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Knockdown Techniques</subject><subject>Health risks</subject><subject>Heart diseases</subject><subject>Hemangioblasts</subject><subject>Hemangioblasts - cytology</subject><subject>Hemangioblasts - metabolism</subject><subject>Hematopoiesis</subject><subject>Hematopoiesis - genetics</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Lipoproteins - antagonists & inhibitors</subject><subject>Lipoproteins - genetics</subject><subject>Lipoproteins - metabolism</subject><subject>Myelopoiesis</subject><subject>Myelopoiesis - genetics</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>PU.1 protein</subject><subject>Runx1 protein</subject><subject>Specifications</subject><subject>Stem cells</subject><subject>Tissue factor</subject><subject>vascular development</subject><subject>Zebrafish</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish Proteins - antagonists & inhibitors</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEUhS0EoqGwZYkssWEzwT8z9ngBElQEiiohBVhbjue6cTQzHuyZluyqPgHPyJPgKKFK2bC6i_Pdc38OQs8pmVOixGu3mTNCJSFUiOXyAZrRipNC1II8RDNSK1YIwesT9CSlDclU5h6jE1bXUqpKztDteQP96J23ZvShx8Fhg3u4xqYZ40B_3_wa3eBxhMupNWOIW2x--oRdiHhcA04D2HvNQ_SdH_0V4G4LbRiCh5R50ze4Aef7vbaGLpsdxKfokTNtgmeHeoq-Lz58O_tUXHz5eH727qKwpWTLorGOWLGqqFIKFCuJFFWpBCdOcMqcKoWyjHORnyGl46WoamIbWTJby5VZlfwUvd37DtOqg8bmu6Np9W5jE7c6GK_vK71f68twpSvJKWVVNnh1MIjhxwRp1J1PFtrW9BCmpKniQjBekd2sl_-gmzDFPp-nGSGizv9Xdabme8rGkFIEd7cMJXoXr3YbfRRvbnhxfMId_jfPDLzZA9e-he1_7PTi63u2-Hw84A-ZULXP</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Wang, Li</creator><creator>Wang, Xiaojing</creator><creator>Wang, Longfei</creator><creator>Yousaf, Muhammad</creator><creator>Li, Jia</creator><creator>Zuo, Mengxia</creator><creator>Yang, Zhongcheng</creator><creator>Gou, Dongzhi</creator><creator>Bao, Binghao</creator><creator>Li, Lei</creator><creator>Xiang, Ning</creator><creator>Jia, Haibo</creator><creator>Xu, Chengqi</creator><creator>Chen, Qiuyun</creator><creator>Wang, Qing Kenneth</creator><general>Federation of American Societies for Experimental Biology</general><general>Federation of American Societies for Experimental Biology (FASEB)</general><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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201801</creationdate><title>Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis</title><author>Wang, Li ; Wang, Xiaojing ; Wang, Longfei ; Yousaf, Muhammad ; Li, Jia ; Zuo, Mengxia ; Yang, Zhongcheng ; Gou, Dongzhi ; Bao, Binghao ; Li, Lei ; Xiang, Ning ; Jia, Haibo ; Xu, Chengqi ; Chen, Qiuyun ; Wang, Qing Kenneth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472R-dcf0c6b51999e924076549630f6312f9469c233617077f346580cd742c87bab43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>aggf1</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Biomarkers</topic><topic>c-Myb protein</topic><topic>Cardiovascular disease</topic><topic>Cell Differentiation</topic><topic>coagulation</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - metabolism</topic><topic>Erythropoiesis</topic><topic>GATA-1 protein</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Knockdown Techniques</topic><topic>Health risks</topic><topic>Heart diseases</topic><topic>Hemangioblasts</topic><topic>Hemangioblasts - cytology</topic><topic>Hemangioblasts - metabolism</topic><topic>Hematopoiesis</topic><topic>Hematopoiesis - genetics</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Lipoproteins - antagonists & inhibitors</topic><topic>Lipoproteins - genetics</topic><topic>Lipoproteins - metabolism</topic><topic>Myelopoiesis</topic><topic>Myelopoiesis - genetics</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>PU.1 protein</topic><topic>Runx1 protein</topic><topic>Specifications</topic><topic>Stem cells</topic><topic>Tissue factor</topic><topic>vascular development</topic><topic>Zebrafish</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - antagonists & inhibitors</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Wang, Longfei</creatorcontrib><creatorcontrib>Yousaf, Muhammad</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Zuo, Mengxia</creatorcontrib><creatorcontrib>Yang, Zhongcheng</creatorcontrib><creatorcontrib>Gou, Dongzhi</creatorcontrib><creatorcontrib>Bao, Binghao</creatorcontrib><creatorcontrib>Li, Lei</creatorcontrib><creatorcontrib>Xiang, Ning</creatorcontrib><creatorcontrib>Jia, Haibo</creatorcontrib><creatorcontrib>Xu, Chengqi</creatorcontrib><creatorcontrib>Chen, Qiuyun</creatorcontrib><creatorcontrib>Wang, Qing Kenneth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Li</au><au>Wang, Xiaojing</au><au>Wang, Longfei</au><au>Yousaf, Muhammad</au><au>Li, Jia</au><au>Zuo, Mengxia</au><au>Yang, Zhongcheng</au><au>Gou, Dongzhi</au><au>Bao, Binghao</au><au>Li, Lei</au><au>Xiang, Ning</au><au>Jia, Haibo</au><au>Xu, Chengqi</au><au>Chen, Qiuyun</au><au>Wang, Qing Kenneth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2018-01</date><risdate>2018</risdate><volume>32</volume><issue>1</issue><spage>183</spage><epage>194</epage><pages>183-194</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>A genomic variant in the human ADTRP [androgen‐dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vas‐ culogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrpl and adtrp2). Knockdown of adtrpl expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp, flila, and scl; blocks primitive hematopoiesis, as shown by decreased expression of pu.1, mpo, and l‐plastin; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c‐myb. However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h‐bae1) or vasculogenesis (no effect on kdrl, ephb2a, notch3, dab2, or flt4). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang L., Wang X., Wang L., Yousaf, M., Li, J., Zuo, M., Yang Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang Q. K. Identificationofanew adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis. FASEB J. 32, 183‐194 (2018). www.fasebj.org</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>28877957</pmid><doi>10.1096/fj.201700166RR</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | aggf1 Animals Animals, Genetically Modified Biomarkers c-Myb protein Cardiovascular disease Cell Differentiation coagulation Coronary artery Coronary artery disease Endothelial Cells - cytology Endothelial Cells - metabolism Erythropoiesis GATA-1 protein Gene Expression Regulation, Developmental Gene Knockdown Techniques Health risks Heart diseases Hemangioblasts Hemangioblasts - cytology Hemangioblasts - metabolism Hematopoiesis Hematopoiesis - genetics Hematopoietic stem cells Humans Inhibitors Lipoproteins - antagonists & inhibitors Lipoproteins - genetics Lipoproteins - metabolism Myelopoiesis Myelopoiesis - genetics Neovascularization, Physiologic - genetics PU.1 protein Runx1 protein Specifications Stem cells Tissue factor vascular development Zebrafish Zebrafish - embryology Zebrafish - genetics Zebrafish - metabolism Zebrafish Proteins - antagonists & inhibitors Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis |
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