• 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

Dntt 表达揭示了造血祖细胞的发育层次结构和谱系特化。

Dntt expression reveals developmental hierarchy and lineage specification of hematopoietic progenitors.

机构信息

Department of Biomedicine, University of Basel, Basel, Switzerland.

Swiss Institute of Bioinformatics, Basel, Switzerland.

出版信息

Nat Immunol. 2022 Apr;23(4):505-517. doi: 10.1038/s41590-022-01167-5. Epub 2022 Mar 30.

DOI:10.1038/s41590-022-01167-5
PMID:35354960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9208307/
Abstract

Intrinsic and extrinsic cues determine developmental trajectories of hematopoietic stem cells (HSCs) towards erythroid, myeloid and lymphoid lineages. Using two newly generated transgenic mice that report and trace the expression of terminal deoxynucleotidyl transferase (TdT), transient induction of TdT was detected on a newly identified multipotent progenitor (MPP) subset that lacked self-renewal capacity but maintained multilineage differentiation potential. TdT induction on MPPs reflected a transcriptionally dynamic but uncommitted stage, characterized by low expression of lineage-associated genes. Single-cell CITE-seq indicated that multipotency in the TdT MPPs is associated with expression of the endothelial cell adhesion molecule ESAM. Stable and progressive upregulation of TdT defined the lymphoid developmental trajectory. Collectively, we here identify a new multipotent progenitor within the MPP4 compartment. Specification and commitment are defined by downregulation of ESAM which marks the progressive loss of alternative fates along all lineages.

摘要

内在和外在线索决定了造血干细胞（HSCs）向红细胞、髓样细胞和淋巴样谱系的发育轨迹。使用两种新生成的转基因小鼠，报告和追踪末端脱氧核苷酸转移酶（TdT）的表达，在一个新鉴定的多能祖细胞（MPP）亚群中检测到 TdT 的短暂诱导，该亚群缺乏自我更新能力，但保持多谱系分化潜能。MPP 上的 TdT 诱导反映了一个转录活跃但未决定的阶段，其特征是谱系相关基因的低表达。单细胞 CITE-seq 表明，TdT MPP 中的多能性与内皮细胞粘附分子 ESAM 的表达有关。TdT 的稳定和渐进上调定义了淋巴样发育轨迹。总的来说，我们在这里确定了 MPP4 隔室中的一个新的多能祖细胞。规范和承诺是通过下调 ESAM 来定义的，ESAM 标志着沿着所有谱系丧失替代命运的渐进性丧失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/175f7810238e/nihms-1782537-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/92093773dbcd/nihms-1782537-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/0e7a357b074d/nihms-1782537-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/aba76b72f1e7/nihms-1782537-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/73c21a85e974/nihms-1782537-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/67528fa4b97f/nihms-1782537-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/a0f2861de1ec/nihms-1782537-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/89cc65b2c680/nihms-1782537-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/af3db7cb2245/nihms-1782537-f0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/821ff07893e8/nihms-1782537-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/fac2cb0c86f8/nihms-1782537-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/224ee12ddbbd/nihms-1782537-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/1094d0383d02/nihms-1782537-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/07519e5b9759/nihms-1782537-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/93cfa8493e2c/nihms-1782537-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/175f7810238e/nihms-1782537-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/92093773dbcd/nihms-1782537-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/0e7a357b074d/nihms-1782537-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/aba76b72f1e7/nihms-1782537-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/73c21a85e974/nihms-1782537-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/67528fa4b97f/nihms-1782537-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/a0f2861de1ec/nihms-1782537-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/89cc65b2c680/nihms-1782537-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/af3db7cb2245/nihms-1782537-f0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/821ff07893e8/nihms-1782537-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/fac2cb0c86f8/nihms-1782537-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/224ee12ddbbd/nihms-1782537-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/1094d0383d02/nihms-1782537-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/07519e5b9759/nihms-1782537-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/93cfa8493e2c/nihms-1782537-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b4/9208307/175f7810238e/nihms-1782537-f0007.jpg

相似文献

1
Dntt expression reveals developmental hierarchy and lineage specification of hematopoietic progenitors.Dntt 表达揭示了造血祖细胞的发育层次结构和谱系特化。
Nat Immunol. 2022 Apr;23(4):505-517. doi: 10.1038/s41590-022-01167-5. Epub 2022 Mar 30.
2
Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors.多能造血祖细胞中不对称的淋巴细胞和髓细胞系定向分化
J Exp Med. 2006 Aug 7;203(8):1867-73. doi: 10.1084/jem.20060697. Epub 2006 Jul 31.
3
Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions.谱系偏向多能祖细胞的功能不同亚群在正常和再生条件下控制血液生成。
Cell Stem Cell. 2015 Jul 2;17(1):35-46. doi: 10.1016/j.stem.2015.05.003. Epub 2015 Jun 18.
4
Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.多能造血干细胞的层次相关谱系限制命运。
Nature. 2018 Feb 1;554(7690):106-111. doi: 10.1038/nature25455. Epub 2018 Jan 3.
5
Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.小鼠造血干细胞和多能祖细胞表达c-kit受体的截短型细胞内形式。
Stem Cells Dev. 2008 Apr;17(2):343-53. doi: 10.1089/scd.2007.0101.
6
E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction.E47 调节造血干细胞的增殖和能量代谢，但不调节髓系谱系限制。
Blood. 2011 Mar 31;117(13):3529-38. doi: 10.1182/blood-2010-07-297689. Epub 2011 Jan 27.
7
Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1.多能造血干/祖细胞中多梳蛋白 BMI1 对细胞定型的调控作用。
Cell Stem Cell. 2010 Mar 5;6(3):279-86. doi: 10.1016/j.stem.2010.01.005.
8
SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors.SLAM 家族标志物可区分造血干细胞和多能祖细胞的功能不同的亚群。
Cell Stem Cell. 2013 Jul 3;13(1):102-16. doi: 10.1016/j.stem.2013.05.014.
9
Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.多能造血祖细胞的渐进性改变是衰老过程中淋巴细胞丢失的基础。
J Exp Med. 2016 Oct 17;213(11):2259-2267. doi: 10.1084/jem.20160168. Epub 2016 Oct 10.
10
Lineage tracking to reveal the fate of hematopoietic stem cells influenced by Flk2 multipotent progenitors after transplantation.谱系追踪揭示移植后受 Flk2 多能祖细胞影响的造血干细胞的命运。
Exp Mol Med. 2023 Jan;55(1):205-214. doi: 10.1038/s12276-022-00922-w. Epub 2023 Jan 13.

引用本文的文献

1
Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.细胞与组织重编程：开启药物研发的新时代。
Pharmacol Rev. 2025 Jun 26;77(5):100077. doi: 10.1016/j.pharmr.2025.100077.
2
CellMemory: hierarchical interpretation of out-of-distribution cells using bottlenecked transformer.细胞记忆：使用瓶颈变压器对分布外细胞进行分层解释。
Genome Biol. 2025 Jun 23;26(1):178. doi: 10.1186/s13059-025-03638-y.
3
Defining 2 biologically and clinically distinct groups in acute leukemia with a mixed phenotype.定义具有混合表型的急性白血病中两个生物学和临床特征不同的组。

本文引用的文献

1
Integrated analysis of multimodal single-cell data.多模态单细胞数据的综合分析。
Cell. 2021 Jun 24;184(13):3573-3587.e29. doi: 10.1016/j.cell.2021.04.048. Epub 2021 May 31.
2
Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells.多能祖细胞 5 号细胞位于造血干细胞和祖细胞的分裂间期。
Blood. 2021 Jun 10;137(23):3218-3224. doi: 10.1182/blood.2020007876.
3
Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis.单细胞谱系追踪揭示了 TCF15 在造血中的作用。
Blood. 2025 May 1;145(18):2056-2069. doi: 10.1182/blood.2024026273.
4
The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.肺癌与骨髓龛之间的串扰促进应急性骨髓造血。
Front Immunol. 2024 Aug 1;15:1397469. doi: 10.3389/fimmu.2024.1397469. eCollection 2024.
5
Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors.末端脱氧核苷酸转移酶和 CD84 可识别人类多能淋巴祖细胞。
Nat Commun. 2024 Jul 13;15(1):5910. doi: 10.1038/s41467-024-49883-w.
6
Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation.核孔蛋白 Nup358 通过调节组蛋白去乙酰化酶 3 的核转位驱动偏骨髓多能祖细胞的分化。
Sci Adv. 2024 Jun 7;10(23):eadn8963. doi: 10.1126/sciadv.adn8963. Epub 2024 Jun 5.
7
Co-staining with Fluorescent Antibodies and Antibody-Derived Tags for Cell Sorting Prior to CITE-Seq.荧光抗体与抗体衍生标签共染色在 CITE-Seq 前进行细胞分选。
Methods Mol Biol. 2024;2779:287-303. doi: 10.1007/978-1-0716-3738-8_13.
8
A time- and single-cell-resolved model of murine bone marrow hematopoiesis.一个时间和单细胞分辨的鼠骨髓造血模型。
Cell Stem Cell. 2024 Feb 1;31(2):244-259.e10. doi: 10.1016/j.stem.2023.12.001. Epub 2024 Jan 5.
9
Regulation of pDC fate determination by histone deacetylase 3.组蛋白去乙酰化酶 3 对浆细胞样树突状细胞命运决定的调控。
Elife. 2023 Nov 27;12:e80477. doi: 10.7554/eLife.80477.
10
Regulation of lymphoid-myeloid lineage bias through regnase-1/3-mediated control of Nfkbiz.通过 Regnase-1/3 介导的 Nfkbiz 控制调节淋巴样髓系谱系偏向
Blood. 2024 Jan 18;143(3):243-257. doi: 10.1182/blood.2023020903.
Nature. 2020 Jul;583(7817):585-589. doi: 10.1038/s41586-020-2503-6. Epub 2020 Jul 15.
4
Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis.通过单细胞转录组分析追踪移植造血干细胞的分化。
Nat Cell Biol. 2020 Jun;22(6):630-639. doi: 10.1038/s41556-020-0512-1. Epub 2020 May 4.
5
Orchestrating single-cell analysis with Bioconductor.使用 Bioconductor 进行单细胞分析的协调。
Nat Methods. 2020 Feb;17(2):137-145. doi: 10.1038/s41592-019-0654-x. Epub 2019 Dec 2.
6
Plasmacytoid dendritic cells develop from Ly6D lymphoid progenitors distinct from the myeloid lineage.浆细胞样树突状细胞来源于不同于髓系的 Ly6D 淋巴祖细胞。
Nat Immunol. 2019 Jul;20(7):852-864. doi: 10.1038/s41590-019-0420-3. Epub 2019 Jun 18.
7
Comprehensive Integration of Single-Cell Data.单细胞数据的综合整合。
Cell. 2019 Jun 13;177(7):1888-1902.e21. doi: 10.1016/j.cell.2019.05.031. Epub 2019 Jun 6.
8
A comparison of single-cell trajectory inference methods.单细胞轨迹推断方法比较。
Nat Biotechnol. 2019 May;37(5):547-554. doi: 10.1038/s41587-019-0071-9. Epub 2019 Apr 1.
9
The single-cell transcriptional landscape of mammalian organogenesis.哺乳动物器官发生的单细胞转录组图谱。
Nature. 2019 Feb;566(7745):496-502. doi: 10.1038/s41586-019-0969-x. Epub 2019 Feb 20.
10
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.转录因子 Duxbl 介导β选择失败的前 T 细胞的消除。
J Exp Med. 2019 Mar 4;216(3):638-655. doi: 10.1084/jem.20181444. Epub 2019 Feb 14.