2022年3月16日 · Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of Tpo reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs.

TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO signaling associated with bone marrow failure and thrombocytopenia. Recent studies have shown that constitutive activation mutations in Mpl contribute to myeloproliferative disease.

2020年3月3日 · Thrombopoietin (TPO) is an important stimulator and clinical drug for promoting megakaryopoiesis and platelet production. 8-14 Additionally, TPO has been proved to exert critical function on hematopoietic stem cells (HSCs), which can activate the c-MPL receptor on HSCs and regulate hematopoiesis, HSC self-renewal, and quiescence. 12 Exogenous ...

HSCs also requires TPO for its survival, self-renewal, and platelet production during differentiating into megakaryocytes . TPO acts via its myeloproliferative leukemia receptor ( 17 ). Numerous types of media and supplements have been exploited in various HSCs studies to maintain self-renewal, proliferation, and culture HSCs under in vitro ...

2018年4月6日 · We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells.

2023年8月25日 · Thrombopoietin (THPO or TPO) is a class I cytokine essential for hematopoietic stem cell (HSC) maintenance 1, 2 and is the primary driver of megakaryocyte differentiation and platelet production. 3, 4, 5 Dysregulation of TPO and the TPO receptor (TpoR or MPL) leads to disease states, with loss-of-function (LOF) mutations leading to ...

2019年5月29日 · To optimize HSC cultures, we initially titrated thrombopoietin (TPO) against stem-cell factor (SCF) in seven-day CD34 − c-KIT + SCA1 + Lineage (Lin) − (CD34 − KSL) HSC cultures (Extended Data...

2011年5月15日 · Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation nee …

Thrombopoietin (TPO) and its receptor, MPL, are the primary regulators of platelet production and critical for hematopoietic stem cell (HSC) maintenance. Since TPO was first cloned in 1994, the physiological and pathological roles of TPO and MPL ...

2020年12月31日 · Thrombopoietin (TPO) and the TPO-receptor (TPO-R, or c-MPL) are essential for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Agents that can modulate TPO-R signaling are highly desirable for both basic research and clinical utility.

造血干细胞（hematopoietic stem cell, HSC）是一类成体组织干细胞，通过定向分化产生淋系和髓系等造血祖细胞，进而大量增殖分化成各类成熟的功能性血细胞以维持整个机体的造血稳态。HSC具有自我更新、多系分化、凋亡、运动迁徙和保持静息等生物学特性。

近年来研究发现，TPO 对造血 干细胞(HSC)的自我更新和增殖分化等功能具有调控作用， 且随着研究的不断深入，对TPO 调节免疫细胞生成的作用 机制也有了新的认识。 该文围绕TPO 对造血干细胞功能、 血小板生成、免疫细胞生成的作用及机制研究展开综述。 关键词 血小板生成素;造血干细胞;血小板生成;免疫细胞 中图分类号 R 331. 23 文献标志码A 文章编号1000 －1492(2023)03 －0519 －04 doi:10．19405/j． cnki． issn1000 －1492．2023．03．030.

2010年12月14日 · Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-med …

2024年3月11日 · HSC的负向调控因子（TGF-β、MIP-1α、p38）主要在细胞周期关卡（checkpoint）进行调节，抑制细胞进入G0期。 而一些 HSC 正向调控因子（SCF、FL3、TPO）可以使细胞走出G0期，开始扩增 ，因而在HSC的培养过程中，细胞因子的选择至关重要。

2014年1月23日 · TPO signals in HSCs. TPO is essential for the maintenance of HSCs mediated by regulation of a variety of signaling molecules that are involved in cell cycle, survival, cellular metabolism, and integrin-mediated signal transduction. ERK and NF-κB collaborate to repair IR-induced DNA damage under TPO stimulation, preventing aging and tumorigenesis.

2020年1月8日 · Here, we describe a simple platform for the expansion of functional mouse HSCs ex vivo for >1 month under fully defined albumin-free conditions. The culture system affords 236- to 899-fold...

2024年2月13日 · Marrow and splenic HSCs exhibited different responses to TPO/MPL ablation and exogenous TPO treatment. Splenic niche cells compensated for marrow HSC loss in TPO −/− and MPL −/− mice by upregulating CXCL12 levels. These findings provide new insights into the complex regulation of HSCs by TPO/MPL and reveal a previously unknown link ...

2024年9月20日 · 造血干细胞（hematopoietic stem cell, HSPC）是一类成体组织干细胞，其功能定义是具有自我更新（即通过细胞分裂产生子代HSPC）和多能分化（即产生任何成熟的成人造血细胞类型）潜力的细胞。 因其独特的生物学特性，目前HSPC的应用被分为两个方向：一是利用HSPC的自我更新、运动迁移等能力，用干细胞进行回输治疗而发展出的干细胞移植技术和干细胞基因治疗，目前这两种技术已被用于治疗血液系统良恶性疾病、实体肿瘤（如视神经母细胞 …

Through systematic optimization, we have found that high thrombopoietin (TPO) synergizes with low stem cell factor (SCF) and fibronectin to sustain HSC self-renewal. Furthermore, we identified polyvinyl alcohol (PVA) as a functionally-superior, Good Manufacturing Practice (GMP)-compatible replacement for serum albumin, which has long been a ...

血小板生成素（thpo 或 tpo）是造血干细胞（hsc）维持和巨核细胞分化的重要细胞因子。 在这里，我们报道了细胞外 TPO-TPO 受体（TpoR 或 MPL）信号复合物的 3.4 Å 分辨率冷冻电子显微镜结构，揭示了同二聚体 MPL 激活的基础，并为遗传功能丧失性血小板减少症突变 ...