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造血心形成类器官再现了人类造血系统和胚胎心脏的共同发育。

Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart.

机构信息

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Research Core Unit Genomics (RCUG), Hannover Medical School, Hannover, Germany.

出版信息

Nat Cell Biol. 2024 Nov;26(11):1984-1996. doi: 10.1038/s41556-024-01526-4. Epub 2024 Oct 8.

DOI:10.1038/s41556-024-01526-4
PMID:39379702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11567889/
Abstract

Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.

摘要

尽管造血干细胞和造血祖细胞具有重要的生物医学意义，但由于对指定多个造血波的信号和标记的了解有限，以及对人类胚胎的伦理限制，它们在体外的稳定状态尚未实现。因此，类似于在邻近组织背景下进行造血发育的体外方法引起了人们的兴趣。我们已建立的人类多能干细胞衍生的心脏类器官（HFO）重现了心脏、血管和前肠共同发育的多个方面。在调节 HFO 分化的过程中，我们在此报告了造血 HFO 的产生。在维持具有功能性心室样心脏原基的同时，造血 HFO 包含一个嵌入间充质的造血内皮层，包含多个具有红髓-骨髓和淋巴样潜能的造血衍生物和造血祖细胞，反映了原始和定型造血的多个方面。该模型能够实现心脏、内皮和多能造血组织的形态结构共发育，相当于体内胚胎内造血区域，促进了体外造血研究。

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2
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Signal Transduct Target Ther. 2023 Jun 2;8(1):230. doi: 10.1038/s41392-023-01455-y.
3
Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.
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4
Guided Differentiation of Pluripotent Stem Cells into Heterogeneously Differentiating Cultures of Cardiac Cells.多能干细胞向异质性分化的心肌细胞培养物的定向分化
bioRxiv. 2025 Feb 19:2023.07.21.550072. doi: 10.1101/2023.07.21.550072.
心外膜单细胞基因组学揭示了人类心外膜在心脏发育和疾病中的生物学原理。
Nat Biotechnol. 2023 Dec;41(12):1787-1800. doi: 10.1038/s41587-023-01718-7. Epub 2023 Apr 3.
4
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Cancer Discov. 2023 Feb 6;13(2):364-385. doi: 10.1158/2159-8290.CD-22-0199.
5
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6
Gastruloids as in vitro models of embryonic blood development with spatial and temporal resolution.具有时空分辨率的体外胚胎血液发育的类囊胚模型。
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7
Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data.单细胞 RNA-Seq 数据中细胞间通讯推断方法和资源的比较。
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8
Mapping human haematopoietic stem cells from haemogenic endothelium to birth.从造血内皮细胞到出生的人类造血干细胞映射
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9
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10
Generation of heart-forming organoids from human pluripotent stem cells.从人类多能干细胞生成心脏类器官。
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