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Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells
Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, w...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2013-11, Vol.110 (47), p.18892-18897 |
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| Main Authors: | , , , , , |
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| cites | cdi_FETCH-LOGICAL-c591t-2fbc04fa132ebee54e0bf505f7ceaaeb81148b57483506c241cba20c6257e0003 |
| container_end_page | 18897 |
| container_issue | 47 |
| container_start_page | 18892 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 110 |
| creator | Shin, Jae-Won Spinler, Kyle R. Swift, Joe Chasis, Joel A. Mohandas, Narla Discher, Dennis E. |
| description | Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34 ⁺ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. In particular, erythroid differentiation is promoted by high lamin-A and low lamin-B1 expression whereas megakaryocytes of high ploidy are inhibited by lamin suppression. Lamins thus contribute to both trafficking and differentiation. |
| doi_str_mv | 10.1073/pnas.1304996110 |
| format | article |
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Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34 ⁺ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. In particular, erythroid differentiation is promoted by high lamin-A and low lamin-B1 expression whereas megakaryocytes of high ploidy are inhibited by lamin suppression. Lamins thus contribute to both trafficking and differentiation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1304996110</identifier><identifier>PMID: 24191023</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adult Stem Cells - cytology ; Adult Stem Cells - physiology ; adults ; Biological Sciences ; Biophysics ; Blood ; Blood cells ; Bone marrow ; Cell Lineage - physiology ; Cell lines ; Cell Movement - physiology ; Cell nucleus ; Cell Nucleus - metabolism ; erythroblasts ; Erythropoiesis - physiology ; Flow cytometry ; Flow Cytometry - methods ; gene overexpression ; Hematopoietic stem cells ; Humans ; Lamins ; Lamins - metabolism ; Mass spectrometry ; Mass Spectrometry - methods ; megakaryocytes ; micropores ; Physical Sciences ; ploidy ; porous media ; Progenitor cells ; Proteins ; retinoic acid ; Rheology ; Stem cells ; stoichiometry ; T lymphocytes ; Thrombopoiesis - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-11, Vol.110 (47), p.18892-18897</ispartof><rights>copyright © 1993—2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 19, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-2fbc04fa132ebee54e0bf505f7ceaaeb81148b57483506c241cba20c6257e0003</citedby><cites>FETCH-LOGICAL-c591t-2fbc04fa132ebee54e0bf505f7ceaaeb81148b57483506c241cba20c6257e0003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/47.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23756814$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23756814$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768,58213,58446</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24191023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shin, Jae-Won</creatorcontrib><creatorcontrib>Spinler, Kyle R.</creatorcontrib><creatorcontrib>Swift, Joe</creatorcontrib><creatorcontrib>Chasis, Joel A.</creatorcontrib><creatorcontrib>Mohandas, Narla</creatorcontrib><creatorcontrib>Discher, Dennis E.</creatorcontrib><title>Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34 ⁺ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. 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Lamins thus contribute to both trafficking and differentiation.</description><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - physiology</subject><subject>adults</subject><subject>Biological Sciences</subject><subject>Biophysics</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Bone marrow</subject><subject>Cell Lineage - physiology</subject><subject>Cell lines</subject><subject>Cell Movement - physiology</subject><subject>Cell nucleus</subject><subject>Cell Nucleus - metabolism</subject><subject>erythroblasts</subject><subject>Erythropoiesis - physiology</subject><subject>Flow cytometry</subject><subject>Flow Cytometry - methods</subject><subject>gene overexpression</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Lamins</subject><subject>Lamins - metabolism</subject><subject>Mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>megakaryocytes</subject><subject>micropores</subject><subject>Physical Sciences</subject><subject>ploidy</subject><subject>porous media</subject><subject>Progenitor cells</subject><subject>Proteins</subject><subject>retinoic acid</subject><subject>Rheology</subject><subject>Stem cells</subject><subject>stoichiometry</subject><subject>T lymphocytes</subject><subject>Thrombopoiesis - physiology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkb1vFDEUxC0EIpdATQVYSkOzyXu296uJhCK-pJMoIA2N5fXZez527cPeReK_x8sdF6ChcjG_N5rxEPIM4Qqh5td7r9IVchBtWyHCA7JCaLGoRAsPyQqA1UUjmDgj5yntAKAtG3hMzpjAFoHxFfmyVqPziUbTz4OaDNVmGOgUlbVOf3W-p8pv6OC8Ub2ho5rmqCYXPA2Wqs08THQ7j8rTrcla2AdnJqd_maQn5JFVQzJPj-8FuXv75vPt-2L98d2H29frQpctTgWznQZhFXJmOmNKYaCzJZS21kYp0zWIounKWjS8hErn6LpTDHTFytrkSvyC3Bx893M3mo02Pscf5D66UcUfMign_1a828o-fJe84W1dLgavjgYxfJtNmuTo0lJBeRPmJLEBjgzaqvk_KirkQgCvMnr5D7oLc_T5JxYq1-CV4Jm6PlA6hpSisafcCHKZWC4Ty_uJ88WLP-ue-N-bZoAegeXyZJf9RJ27NC3LyPMDsktTiPcWvC6rBkXWXx50q4JUfXRJ3n1igBUACqxzx5_IjcAS</recordid><startdate>20131119</startdate><enddate>20131119</enddate><creator>Shin, Jae-Won</creator><creator>Spinler, Kyle R.</creator><creator>Swift, Joe</creator><creator>Chasis, Joel A.</creator><creator>Mohandas, Narla</creator><creator>Discher, Dennis E.</creator><general>National Academy of Sciences</general><general>NATIONAL ACADEMY OF SCIENCES</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</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>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20131119</creationdate><title>Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells</title><author>Shin, Jae-Won ; 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Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34 ⁺ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-11, Vol.110 (47), p.18892-18897 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | PubMed Central; JSTOR Journals and Primary Sources |
| subjects | Adult Stem Cells - cytology Adult Stem Cells - physiology adults Biological Sciences Biophysics Blood Blood cells Bone marrow Cell Lineage - physiology Cell lines Cell Movement - physiology Cell nucleus Cell Nucleus - metabolism erythroblasts Erythropoiesis - physiology Flow cytometry Flow Cytometry - methods gene overexpression Hematopoietic stem cells Humans Lamins Lamins - metabolism Mass spectrometry Mass Spectrometry - methods megakaryocytes micropores Physical Sciences ploidy porous media Progenitor cells Proteins retinoic acid Rheology Stem cells stoichiometry T lymphocytes Thrombopoiesis - physiology |
| title | Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells |
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