Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver
Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoiet...
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| Veröffentlicht in: | Science advances 2022-03, Vol.8 (11), p.eabm7688-eabm7688 |
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| creator | Lee, Yeojin DiMaulo-Milk, Emily Leslie, Juliana Ding, Lei |
| description | Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of
reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in
mice. Enforced activation of the mTOR pathway by conditionally deleting
significantly rescued HSCs and their gene expression in
mice.
intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of
further reduced mTOR activity and strongly exacerbated HSC depletion in
mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver. |
| doi_str_mv | 10.1126/sciadv.abm7688 |
| format | Article |
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reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in
mice. Enforced activation of the mTOR pathway by conditionally deleting
significantly rescued HSCs and their gene expression in
mice.
intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of
further reduced mTOR activity and strongly exacerbated HSC depletion in
mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abm7688</identifier><identifier>PMID: 35294228</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Biomedicine and Life Sciences ; Cell Biology ; Cell Differentiation ; Developmental Biology ; Hematopoietic Stem Cells ; Liver - metabolism ; Mice ; SciAdv r-articles ; Thrombopoietin - genetics ; Thrombopoietin - metabolism ; Thrombopoietin - pharmacology</subject><ispartof>Science advances, 2022-03, Vol.8 (11), p.eabm7688-eabm7688</ispartof><rights>Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2022 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-65660037149a219a247decb0959a936ec429d382f2ee491f55685c945eec3a1d3</citedby><cites>FETCH-LOGICAL-c390t-65660037149a219a247decb0959a936ec429d382f2ee491f55685c945eec3a1d3</cites><orcidid>0000-0001-9741-3554 ; 0000-0003-4869-8877</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926339/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926339/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35294228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Yeojin</creatorcontrib><creatorcontrib>DiMaulo-Milk, Emily</creatorcontrib><creatorcontrib>Leslie, Juliana</creatorcontrib><creatorcontrib>Ding, Lei</creatorcontrib><title>Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of
reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in
mice. Enforced activation of the mTOR pathway by conditionally deleting
significantly rescued HSCs and their gene expression in
mice.
intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of
further reduced mTOR activity and strongly exacerbated HSC depletion in
mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver.</description><subject>Animals</subject><subject>Biomedicine and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Differentiation</subject><subject>Developmental Biology</subject><subject>Hematopoietic Stem Cells</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>SciAdv r-articles</subject><subject>Thrombopoietin - genetics</subject><subject>Thrombopoietin - metabolism</subject><subject>Thrombopoietin - pharmacology</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1LxDAQDaKorF49So5eds13m4sgi18geNGrIU2nbqRtapJd2H9vl62ih2FmmDdvHvMQuqBkQSlT18l5W28WtuoKVZYH6JTxQs6ZFOXhn_oEnaf0SQihQilJ9TE64ZJpwVh5it4fobM5DMFD9g6nDB120LYJj9UQom3bLc7R9slnH3qcA86rGLpqWulxDQP0NfQO8NjlFeAGsm1x6zcQz9BRY9sE51Oeobf7u9fl4_z55eFpefs8d1yTPFdSKUJ4QYW2jI4hihpcRbTUVnMFTjBd85I1DEBo2kipSum0kACOW1rzGbrZ8w7rqoPaQT9qbs0QfWfj1gTrzf9J71fmI2xMqZniXI8EVxNBDF9rSNl0Pu0eYXsI62SYEoQzoQsyQhd7qIshpQjN7xlKzM4Xs_fFTL6MC5d_xf3Cf1zg3yS2jaE</recordid><startdate>20220318</startdate><enddate>20220318</enddate><creator>Lee, Yeojin</creator><creator>DiMaulo-Milk, Emily</creator><creator>Leslie, Juliana</creator><creator>Ding, Lei</creator><general>American Association for the Advancement of Science</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9741-3554</orcidid><orcidid>https://orcid.org/0000-0003-4869-8877</orcidid></search><sort><creationdate>20220318</creationdate><title>Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver</title><author>Lee, Yeojin ; DiMaulo-Milk, Emily ; Leslie, Juliana ; Ding, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-65660037149a219a247decb0959a936ec429d382f2ee491f55685c945eec3a1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Biomedicine and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Differentiation</topic><topic>Developmental Biology</topic><topic>Hematopoietic Stem Cells</topic><topic>Liver - metabolism</topic><topic>Mice</topic><topic>SciAdv r-articles</topic><topic>Thrombopoietin - genetics</topic><topic>Thrombopoietin - metabolism</topic><topic>Thrombopoietin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Yeojin</creatorcontrib><creatorcontrib>DiMaulo-Milk, Emily</creatorcontrib><creatorcontrib>Leslie, Juliana</creatorcontrib><creatorcontrib>Ding, Lei</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Yeojin</au><au>DiMaulo-Milk, Emily</au><au>Leslie, Juliana</au><au>Ding, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2022-03-18</date><risdate>2022</risdate><volume>8</volume><issue>11</issue><spage>eabm7688</spage><epage>eabm7688</epage><pages>eabm7688-eabm7688</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of
reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in
mice. Enforced activation of the mTOR pathway by conditionally deleting
significantly rescued HSCs and their gene expression in
mice.
intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of
further reduced mTOR activity and strongly exacerbated HSC depletion in
mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>35294228</pmid><doi>10.1126/sciadv.abm7688</doi><orcidid>https://orcid.org/0000-0001-9741-3554</orcidid><orcidid>https://orcid.org/0000-0003-4869-8877</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biomedicine and Life Sciences Cell Biology Cell Differentiation Developmental Biology Hematopoietic Stem Cells Liver - metabolism Mice SciAdv r-articles Thrombopoietin - genetics Thrombopoietin - metabolism Thrombopoietin - pharmacology |
| title | Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver |
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