• 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

从人多能干细胞中鉴定出依赖维甲酸的造血内皮祖细胞。

Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells.

机构信息

Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, USA.

Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Nat Cell Biol. 2022 May;24(5):616-624. doi: 10.1038/s41556-022-00898-9. Epub 2022 Apr 28.

DOI:10.1038/s41556-022-00898-9
PMID:35484246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9109599/
Abstract

The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine. During embryonic development, HSCs derive from haemogenic endothelium (HE) in a NOTCH- and retinoic acid (RA)-dependent manner. Although a WNT-dependent (WNTd) patterning of nascent hPSC mesoderm specifies clonally multipotent intra-embryonic-like HOXA definitive HE, this HE is functionally unresponsive to RA. Here we show that WNTd mesoderm, before HE specification, is actually composed of two distinct KDR CD34 populations. CXCR4CYP26A1 mesoderm gives rise to HOXA multilineage definitive HE in an RA-independent manner, whereas CXCR4 ALDH1A2 mesoderm gives rise to HOXA multilineage definitive HE in a stage-specific, RA-dependent manner. Furthermore, both RA-independent (RAi) and RA-dependent (RAd) HE harbour transcriptional similarity to distinct populations found in the early human embryo, including HSC-competent HE. This revised model of human haematopoietic development provides essential resolution to the regulation and origins of the multiple waves of haematopoiesis. These insights provide the basis for the generation of specific haematopoietic populations, including the de novo specification of HSCs.

摘要

从人类多能干细胞 (hPSC) 中生成造血干细胞 (HSC) 是再生医学的主要目标。在胚胎发育过程中，HSC 来源于以 NOTCH 和视黄酸 (RA) 依赖的方式产生的造血内皮 (HE)。尽管新生 hPSC 中胚层的 WNT 依赖性 (WNTd) 模式化指定了克隆多能性胚胎内样 HOXA 确定性 HE，但这种 HE 对 RA 无功能反应。在这里，我们表明，在 HE 特异性之前，WNTd 中胚层实际上由两个不同的 KDR CD34 群体组成。CXCR4CYP26A1 中胚层以 RA 独立的方式产生 HOXA 多谱系确定性 HE，而 CXCR4 ALDH1A2 中胚层以特定阶段、RA 依赖的方式产生 HOXA 多谱系确定性 HE。此外，RA 独立 (RAi) 和 RA 依赖 (RAd) HE 与在早期人类胚胎中发现的不同群体具有转录相似性，包括具有造血干细胞能力的 HE。这种对人类造血发育的修正模型为多个造血波的调控和起源提供了必要的分辨率。这些见解为特定造血群体的产生提供了基础，包括 HSC 的从头指定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/fc1600eb5f1a/nihms-1790103-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/ea63aa8e2160/nihms-1790103-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/6a0390922909/nihms-1790103-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/e7ac9a51fc96/nihms-1790103-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/d35798d77d9b/nihms-1790103-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/72ce5b7bf9f5/nihms-1790103-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/8060ac712819/nihms-1790103-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/7b9aec660fbe/nihms-1790103-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/b196af6e7b84/nihms-1790103-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/86c9e6846351/nihms-1790103-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/1b93e92699ad/nihms-1790103-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/b590833da980/nihms-1790103-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/3a633b5c3ff1/nihms-1790103-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/fc1600eb5f1a/nihms-1790103-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/ea63aa8e2160/nihms-1790103-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/6a0390922909/nihms-1790103-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/e7ac9a51fc96/nihms-1790103-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/d35798d77d9b/nihms-1790103-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/72ce5b7bf9f5/nihms-1790103-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/8060ac712819/nihms-1790103-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/7b9aec660fbe/nihms-1790103-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/b196af6e7b84/nihms-1790103-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/86c9e6846351/nihms-1790103-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/1b93e92699ad/nihms-1790103-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/b590833da980/nihms-1790103-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/3a633b5c3ff1/nihms-1790103-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c0/9109599/fc1600eb5f1a/nihms-1790103-f0004.jpg

相似文献

1
Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells.从人多能干细胞中鉴定出依赖维甲酸的造血内皮祖细胞。
Nat Cell Biol. 2022 May;24(5):616-624. doi: 10.1038/s41556-022-00898-9. Epub 2022 Apr 28.
2
Stem cell insights into human trophoblast lineage differentiation.干细胞对人类滋养层谱系分化的研究。
Hum Reprod Update. 2016 Dec;23(1):77-103. doi: 10.1093/humupd/dmw026. Epub 2016 Sep 2.
3
CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential.CD1d 表达标志着具有明确造血潜能的 CDX4+ 造血中胚层。
Stem Cell Res. 2022 Jul;62:102808. doi: 10.1016/j.scr.2022.102808. Epub 2022 May 8.
4
Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages.人类确定性造血内皮细胞和动脉血管内皮细胞代表不同的谱系。
Nat Cell Biol. 2015 May;17(5):580-91. doi: 10.1038/ncb3161. Epub 2015 Apr 27.
5
Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation.维甲酸巩固治疗用于接受自体造血干细胞移植的高危神经母细胞瘤患者。
Cochrane Database Syst Rev. 2017 Aug 25;8(8):CD010685. doi: 10.1002/14651858.CD010685.pub3.
6
Effect of retinoic acid treatment on the retinoic acid signaling pathway in a human siRNA-based aniridia limbal epithelial cell model, in vitro.视黄酸处理对体外人源基于小干扰RNA的无虹膜角膜缘上皮细胞模型中视黄酸信号通路的影响。
PLoS One. 2025 Jun 18;20(6):e0324946. doi: 10.1371/journal.pone.0324946. eCollection 2025.
7
Effects of Bisphenol A and Retinoic Acid Exposure on Neuron and Brain Formation: A Study in Human Induced Pluripotent Stem Cells and Zebrafish Embryos.双酚A和视黄酸暴露对神经元和脑形成的影响：一项关于人类诱导多能干细胞和斑马鱼胚胎的研究。
Environ Health Perspect. 2025 Jun;133(6):67012. doi: 10.1289/EHP15574. Epub 2025 Jun 13.
8
Retinoic acid receptor assembly dynamics governs dual functions in cochlear organogenesis.维甲酸受体组装动力学在耳蜗器官发生中发挥双重作用。
Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2426739122. doi: 10.1073/pnas.2426739122. Epub 2025 Jun 27.
9
Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.对接受辅助生殖的不育女性进行宫内注射人绒毛膜促性腺激素（hCG）。
Cochrane Database Syst Rev. 2016 May 20(5):CD011537. doi: 10.1002/14651858.CD011537.pub2.
10
NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells.NOTCH 信号从人多能干细胞中指定动脉型确定性造血内皮细胞。
Nat Commun. 2018 May 8;9(1):1828. doi: 10.1038/s41467-018-04134-7.

引用本文的文献

1
WNT signaling in human pluripotent stem cells promotes HDAC2-dependent epigenetic programs and development of retinoic acid-responsive mesoderm.人类多能干细胞中的WNT信号传导促进了依赖HDAC2的表观遗传程序以及视黄酸反应性中胚层的发育。
bioRxiv. 2025 Jun 8:2025.06.06.657928. doi: 10.1101/2025.06.06.657928.
2
Multimodal analysis of hematopoiesis reveals blood cell-specific genetic impacts on complex disease traits.造血作用的多模态分析揭示了血细胞特异性基因对复杂疾病性状的影响。
bioRxiv. 2025 May 27:2025.05.23.655825. doi: 10.1101/2025.05.23.655825.
3
Bloodhounds chasing the origin of blood cells.

本文引用的文献

1
Single-cell transcriptomic characterization of a gastrulating human embryo.人类囊胚的单细胞转录组特征分析。
Nature. 2021 Dec;600(7888):285-289. doi: 10.1038/s41586-021-04158-y. Epub 2021 Nov 17.
2
Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo.多能祖细胞和造血干细胞在小鼠胚胎中独立于造血内皮产生。
Cell Rep. 2021 Sep 14;36(11):109675. doi: 10.1016/j.celrep.2021.109675.
3
mitch: multi-contrast pathway enrichment for multi-omics and single-cell profiling data.
寻血猎犬追踪血细胞的起源。
Trends Cell Biol. 2025 Apr 10. doi: 10.1016/j.tcb.2025.03.003.
4
Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells.胎盘造血内皮细胞向造血干细胞和祖细胞的转化。
Cell Discov. 2025 Jan 28;11(1):9. doi: 10.1038/s41421-024-00760-2.
5
Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.从多能干细胞生成HLF+HOXA+人类造血祖细胞的方案。
STAR Protoc. 2025 Mar 21;6(1):103592. doi: 10.1016/j.xpro.2024.103592. Epub 2025 Jan 24.
6
The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development.白血病发展过程中克隆进化、分化层次和个体发生的交叉点
Blood Cancer Discov. 2025 Mar 4;6(2):94-109. doi: 10.1158/2643-3230.BCD-24-0235.
7
Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells.诱导多能干细胞向内皮细胞-造血细胞转变的发育调控
bioRxiv. 2024 Nov 22:2024.09.24.612755. doi: 10.1101/2024.09.24.612755.
8
Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis.高效生成表达人 NOTCH 配体的造血内皮细胞，作为体外造血和淋巴发生的基础。
Nat Commun. 2024 Sep 4;15(1):7698. doi: 10.1038/s41467-024-51974-7.
9
Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells.长期植入由人类诱导多能干细胞分化而来的多谱系造血细胞。
Nat Biotechnol. 2024 Sep 2. doi: 10.1038/s41587-024-02360-7.
10
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development.IκBα 通过视黄酸在胚胎发育过程中控制造血干细胞的休眠。
Nat Commun. 2024 Jun 1;15(1):4673. doi: 10.1038/s41467-024-48854-5.
米奇：多组学和单细胞分析数据的多对照通路富集分析。
BMC Genomics. 2020 Jun 29;21(1):447. doi: 10.1186/s12864-020-06856-9.
4
Developmental trajectory of prehematopoietic stem cell formation from endothelium.内皮细胞向造血前体细胞形成的发育轨迹。
Blood. 2020 Aug 13;136(7):845-856. doi: 10.1182/blood.2020004801.
5
Embryonic endothelial evolution towards first hematopoietic stem cells revealed by single-cell transcriptomic and functional analyses.单细胞转录组学和功能分析揭示胚胎内皮细胞向首个造血干细胞的演变过程。
Cell Res. 2020 May;30(5):376-392. doi: 10.1038/s41422-020-0300-2. Epub 2020 Mar 20.
6
Potently Cytotoxic Natural Killer Cells Initially Emerge from Erythro-Myeloid Progenitors during Mammalian Development.在哺乳动物发育过程中，具有强大细胞毒性的自然杀伤细胞最初从红细胞-髓样祖细胞中出现。
Dev Cell. 2020 Apr 20;53(2):229-239.e7. doi: 10.1016/j.devcel.2020.02.016. Epub 2020 Mar 19.
7
Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing.通过单细胞 RNA 测序追踪人类胚胎中的第一个造血干细胞生成。
Cell Res. 2019 Nov;29(11):881-894. doi: 10.1038/s41422-019-0228-6. Epub 2019 Sep 9.
8
Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.基于参考的肺单细胞测序分析揭示了一种过渡性成纤维细胞样巨噬细胞。
Nat Immunol. 2019 Feb;20(2):163-172. doi: 10.1038/s41590-018-0276-y. Epub 2019 Jan 14.
9
RUNX1 and the endothelial origin of blood.RUNX1与血液的内皮起源
Exp Hematol. 2018 Dec;68:2-9. doi: 10.1016/j.exphem.2018.10.009. Epub 2018 Oct 31.
10
Blood Development: Hematopoietic Stem Cell Dependence and Independence.血液发育：造血干细胞的依赖性和独立性。
Cell Stem Cell. 2018 May 3;22(5):639-651. doi: 10.1016/j.stem.2018.04.015.