• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

MEIS1 通过靶向 TAL1 和 FLI1 调控人多能干细胞中的造血内皮生成、巨核细胞生成和血小板生成。

MEIS1 Regulates Hemogenic Endothelial Generation, Megakaryopoiesis, and Thrombopoiesis in Human Pluripotent Stem Cells by Targeting TAL1 and FLI1.

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Tianjin 300020, China; Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin 300020, China.

Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.

出版信息

Stem Cell Reports. 2018 Feb 13;10(2):447-460. doi: 10.1016/j.stemcr.2017.12.017. Epub 2018 Jan 18.

DOI:10.1016/j.stemcr.2017.12.017
PMID:29358086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5830947/
Abstract

Human pluripotent stem cells (hPSCs) provide an unlimited source for generating various kinds of functional blood cells. However, efficient strategies for generating large-scale functional blood cells from hPSCs are still lacking, and the mechanism underlying human hematopoiesis remains largely unknown. In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs). TAL1 mediates the function of MEIS1 in HEP specification. In addition, MEIS1 is vital for megakaryopoiesis and thrombopoiesis from hPSCs. Mechanistically, FLI1 acts as a downstream gene necessary for the function of MEIS1 during megakaryopoiesis. Thus, MEIS1 controls human hematopoiesis in a stage-specific manner and can be potentially manipulated for large-scale generation of HPCs or platelets from hPSCs for therapeutic applications in regenerative medicine.

摘要

人类多能干细胞（hPSCs）为生成各种功能性血细胞提供了无限的来源。然而，从 hPSCs 高效生成大规模功能性血细胞的策略仍然缺乏，人类造血的机制在很大程度上仍然未知。在这项研究中，我们鉴定出髓系异位病毒整合位点 1 同源物（MEIS1）是 hPSC 早期造血分化的关键调节因子。MEIS1 对于 APLNR 中胚层祖细胞向功能性造血内皮祖细胞（HEPs）的特化至关重要，从而控制造血祖细胞（HPCs）的形成。TAL1 介导 MEIS1 在 HEP 特化中的功能。此外，MEIS1 对于 hPSCs 中的巨核细胞生成和血小板生成也是必不可少的。在机制上，FLI1 作为 MEIS1 在巨核细胞生成过程中发挥功能所必需的下游基因。因此，MEIS1 以特定于阶段的方式控制人类造血，可以潜在地操纵 hPSCs 大规模生成 HPCs 或血小板，用于再生医学中的治疗应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/3be197ecb5bd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/5565543ddc3f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/a8618305a81b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/18ad811c28c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/de7096092ad0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/d2a2bfabe82a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/88a35aa731b9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/3be197ecb5bd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/5565543ddc3f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/a8618305a81b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/18ad811c28c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/de7096092ad0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/d2a2bfabe82a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/88a35aa731b9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4d/5830947/3be197ecb5bd/gr7.jpg

相似文献

1
MEIS1 Regulates Hemogenic Endothelial Generation, Megakaryopoiesis, and Thrombopoiesis in Human Pluripotent Stem Cells by Targeting TAL1 and FLI1.MEIS1 通过靶向 TAL1 和 FLI1 调控人多能干细胞中的造血内皮生成、巨核细胞生成和血小板生成。
Stem Cell Reports. 2018 Feb 13;10(2):447-460. doi: 10.1016/j.stemcr.2017.12.017. Epub 2018 Jan 18.
2
MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1.MEIS2 通过靶向 TAL1 调节人胚胎干细胞的内皮向造血转化。
Stem Cell Res Ther. 2018 Dec 7;9(1):340. doi: 10.1186/s13287-018-1074-z.
3
Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression.Meis1 在 Runx1 表达之前建立造血前内皮状态。
Nat Commun. 2023 Jul 27;14(1):4537. doi: 10.1038/s41467-023-40283-0.
4
MEIS1 regulates early erythroid and megakaryocytic cell fate.MEIS1调节早期红系和巨核系细胞命运。
Haematologica. 2014 Oct;99(10):1555-64. doi: 10.3324/haematol.2014.106567. Epub 2014 Aug 8.
5
Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision.经 GATA1、FLI1 和 TAL1 正向编程的人多能干细胞转录因子水平决定巨核细胞与红细胞命运决定。
Stem Cell Reports. 2018 Dec 11;11(6):1462-1478. doi: 10.1016/j.stemcr.2018.11.001. Epub 2018 Nov 29.
6
Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures.鉴定人多能干细胞分化培养中的造血内皮祖细胞及其直接前体细胞。
Cell Rep. 2012 Sep 27;2(3):553-67. doi: 10.1016/j.celrep.2012.08.002. Epub 2012 Sep 13.
7
Congenital thrombocytopenia associated with a heterozygous variant in the gene encoding a transcription factor essential for megakaryopoiesis.先天性血小板减少症与编码巨核细胞生成所必需的转录因子的基因中的杂合变异相关。
Platelets. 2022 May 19;33(4):645-648. doi: 10.1080/09537104.2021.1961704. Epub 2022 Feb 8.
8
Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.成年小鼠红细胞生成、巨核细胞生成和造血干细胞扩增需要Meis1。
PLoS One. 2016 Mar 17;11(3):e0151584. doi: 10.1371/journal.pone.0151584. eCollection 2016.
9
FLI1 level during megakaryopoiesis affects thrombopoiesis and platelet biology.巨核细胞生成过程中的FLI1水平影响血小板生成和血小板生物学。
Blood. 2017 Jun 29;129(26):3486-3494. doi: 10.1182/blood-2017-02-770958. Epub 2017 Apr 21.
10
Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.通过化学限定的正向编程从人多能干细胞大规模生产巨核细胞。
Nat Commun. 2016 Apr 7;7:11208. doi: 10.1038/ncomms11208.

引用本文的文献

1
Enhanced regenerative and developmental potential of embryonal and stem cell-derived platelets compared to adult platelets.与成人血小板相比，胚胎和干细胞来源的血小板具有更强的再生和发育潜力。
Cell Rep Med. 2025 Aug 19;6(8):102297. doi: 10.1016/j.xcrm.2025.102297. Epub 2025 Aug 11.
2
ELTD1 inhibits differentiation of hemogenic endothelium progenitors from human embryonic stem cells through the HPIP-Wnt pathway.ELTD1通过HPIP-Wnt途径抑制人胚胎干细胞来源的造血内皮祖细胞的分化。
Exp Mol Med. 2025 Jun 2. doi: 10.1038/s12276-025-01473-6.
3
Targeting CCR5 with miltefosine as a therapeutic strategy for thrombocytopenia.

本文引用的文献

1
Differentiation of human embryonic stem cells to HOXA hemogenic vasculature that resembles the aorta-gonad-mesonephros.人胚胎干细胞向类似于主动脉-性腺-中肾的 HOXA 血发生血管的分化。
Nat Biotechnol. 2016 Nov;34(11):1168-1179. doi: 10.1038/nbt.3702. Epub 2016 Oct 17.
2
Early Development of Definitive Erythroblasts from Human Pluripotent Stem Cells Defined by Expression of Glycophorin A/CD235a, CD34, and CD36.通过血型糖蛋白A/CD235a、CD34和CD36的表达定义的人多能干细胞向确定红系祖细胞的早期发育
Stem Cell Reports. 2016 Nov 8;7(5):869-883. doi: 10.1016/j.stemcr.2016.09.002. Epub 2016 Oct 6.
3
Generating human hematopoietic stem cells in vitro -exploring endothelial to hematopoietic transition as a portal for stemness acquisition.
以米替福新靶向CCR5作为血小板减少症的治疗策略。
iScience. 2025 Apr 8;28(5):112379. doi: 10.1016/j.isci.2025.112379. eCollection 2025 May 16.
4
Single-nuclei transcriptome analysis of IgM cells isolated from channel catfish () spleen.从斑点叉尾鮰脾脏分离的IgM细胞的单核转录组分析。
Front Immunol. 2025 Mar 17;16:1547193. doi: 10.3389/fimmu.2025.1547193. eCollection 2025.
5
Integrated Multi-Level Investigation of Friend Leukemia Integration 1 Transcription Factor as a Novel Immune-Inflammatory Biomarker in Rheumatoid Arthritis: Bridging Bioinformatics, Clinical Cohorts, and Mechanistic Validation.Friend白血病整合1转录因子作为类风湿性关节炎新型免疫炎症生物标志物的综合多层次研究：连接生物信息学、临床队列和机制验证
J Inflamm Res. 2025 Mar 3;18:3105-3123. doi: 10.2147/JIR.S507941. eCollection 2025.
6
Insight into microRNAs' involvement in hematopoiesis: current standing point of findings.探讨 microRNAs 参与造血过程的研究现状
Stem Cell Res Ther. 2023 Oct 4;14(1):282. doi: 10.1186/s13287-023-03504-3.
7
ZEB2 and MEIS1 independently contribute to hematopoiesis via early hematopoietic enhancer activation.ZEB2和MEIS1通过早期造血增强子激活独立促进造血作用。
iScience. 2023 Sep 9;26(10):107893. doi: 10.1016/j.isci.2023.107893. eCollection 2023 Oct 20.
8
Cross-species transcriptomics reveals bifurcation point during the arterial-to-hemogenic transition.跨物种转录组学揭示了动脉到造血转变过程中的分岔点。
Commun Biol. 2023 Aug 9;6(1):827. doi: 10.1038/s42003-023-05190-6.
9
promotes lateral plate mesoderm formation by modulating the Wnt/β-catenin signaling pathway.通过调节Wnt/β-连环蛋白信号通路促进侧板中胚层的形成。
iScience. 2023 May 19;26(6):106917. doi: 10.1016/j.isci.2023.106917. eCollection 2023 Jun 16.
10
Baffled-flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function.困惑流培养系统通过增强线粒体功能，实现了从人胚胎干细胞中大量生产巨核细胞。
Cell Prolif. 2023 Dec;56(12):e13484. doi: 10.1111/cpr.13484. Epub 2023 Apr 23.
体外生成人类造血干细胞——探索内皮向造血转变作为获得干性的途径。
FEBS Lett. 2016 Nov;590(22):4126-4143. doi: 10.1002/1873-3468.12283. Epub 2016 Jul 22.
4
Deregulation of the HOXA9/MEIS1 axis in acute leukemia.急性白血病中HOXA9/MEIS1轴的失调
Curr Opin Hematol. 2016 Jul;23(4):354-61. doi: 10.1097/MOH.0000000000000245.
5
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.内侧HOXA基因在人类发育过程中界定造血干细胞命运。
Nat Cell Biol. 2016 Jun;18(6):595-606. doi: 10.1038/ncb3354. Epub 2016 May 16.
6
Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.成年小鼠红细胞生成、巨核细胞生成和造血干细胞扩增需要Meis1。
PLoS One. 2016 Mar 17;11(3):e0151584. doi: 10.1371/journal.pone.0151584. eCollection 2016.
7
Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets.了解巨核细胞产生血小板的过程：对体外衍生血小板的意义。
Blood. 2016 Mar 10;127(10):1227-33. doi: 10.1182/blood-2015-08-607929. Epub 2016 Jan 19.
8
MSX2 mediates entry of human pluripotent stem cells into mesendoderm by simultaneously suppressing SOX2 and activating NODAL signaling.MSX2通过同时抑制SOX2并激活NODAL信号传导，介导人类多能干细胞进入中胚层内胚层。
Cell Res. 2015 Dec;25(12):1314-32. doi: 10.1038/cr.2015.118. Epub 2015 Oct 2.
9
GATA2(-/-) human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment.GATA2基因敲除的人胚胎干细胞经历内皮细胞向造血细胞的转变减弱，随后粒细胞定向分化也受到影响。
Cell Regen. 2015 Aug 5;4(1):4. doi: 10.1186/s13619-015-0018-7. eCollection 2015.
10
De novo generation of HSCs from somatic and pluripotent stem cell sources.从体细胞和多能干细胞来源重新生成造血干细胞。
Blood. 2015 Apr 23;125(17):2641-8. doi: 10.1182/blood-2014-10-570234. Epub 2015 Mar 11.