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Tuning of the Hematopoietic Stem Cell Compartment in its Inflammatory Environment. 造血干细胞室在炎症环境中的调节。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-09-01 Epub Date: 2018-07-13 DOI: 10.1007/s40778-018-0131-y
Vinothini Govindarajah, Damien Reynaud

Purpose of review: The hematopoietic stem cell (HSC) compartment is the cornerstone of a lifelong blood cell production but also contributes to the ability of the hematopoietic system to dynamically respond to environmental challenges. This review summarizes our knowledge about the interaction between HSCs and its inflammatory environment during life and questions how its disruption could affect the health of the hematopoietic system.

Recent findings: The latest research demonstrates the direct role of inflammatory signals in promoting the emergence of the HSCs during development and in setting their steady-state activity in adults. They indicate that inflammatory patho-physiological conditions or immunological history could shape the structure and biology of the HSC compartment, therefore altering its overall fitness.

Summary: Through instructive and/or selective mechanisms, the inflammatory environment seems to provide a key homeostatic signal for HSCs. Although the mechanistic basis of this complex interplay remains to be fully understood, its dysregulation has broad consequences on HSC physiology and the development of hematological diseases. As such, developing experimental models that fully recapitulate a normal basal inflammatory state could be essential to fully assess HSC biology in native conditions.

综述目的:造血干细胞(HSC)隔室是终身血细胞生成的基石,但也有助于造血系统动态响应环境挑战的能力。这篇综述总结了我们对造血干细胞与其炎症环境之间相互作用的了解,并对其破坏如何影响造血系统的健康提出了疑问。最新发现:最新研究表明,炎症信号在成人造血干细胞发育过程中促进造血干细胞的出现,并在其稳定活动中发挥直接作用。他们指出,炎症病理生理条件或免疫史可以塑造HSC室的结构和生物学,从而改变其整体适应性。摘要:通过指导性和/或选择性机制,炎症环境似乎为造血干细胞提供了一个关键的稳态信号。尽管这种复杂相互作用的机制基础尚不完全清楚,但其失调对HSC生理和血液病的发展具有广泛的影响。因此,开发完全概括正常基础炎症状态的实验模型对于全面评估自然条件下HSC生物学至关重要。
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引用次数: 2
Clonal Hematopoiesis in Aging. 衰老中的克隆造血。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-09-01 Epub Date: 2018-07-19 DOI: 10.1007/s40778-018-0133-9
Soo J Park, Rafael Bejar

Purpose of review: Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition characterized by the acquisition of somatic mutations. This concise review explores our current understanding of the mechanisms that influence the development of clonality with aging and its potential malignant and non-malignant clinical implications.

Recent findings: Aging of the hematopoietic system results in phenotypic changes that favor clonal dominance. Cell-extrinsic factors provide additional selective pressures that further shape clonal architecture. Even so, small clones with candidate driver mutations appear to be ubiquitous with age and largely benign in the absence of strong selective pressures. Benign clonal expansion may compensate for the loss of regenerative HSC capacity as we age.

Summary: CHIP is a marker of aging that reflects the biologic interplay between HSC aging and cell-extrinsic factors. The clinical significance of CHIP is highly variable and dependent on clinical context. Distinguishing the causal relationships and confounding factors that regulate clonal behavior will be essential to define the mechanistic role of CHIP in aging and potentially mitigate its clinical consequences.

综述目的:克隆性不确定潜能造血(CHIP)是一种常见的、与年龄相关的疾病,其特征是获得体细胞突变。这篇简明的综述探讨了我们目前对影响克隆与衰老发展的机制及其潜在的恶性和非恶性临床意义的理解。最近的发现:造血系统的老化导致表型变化,有利于克隆优势。细胞外部因素提供额外的选择压力,进一步塑造克隆结构。即便如此,具有候选驱动突变的小型克隆似乎随着年龄的增长而普遍存在,而且在缺乏强大的选择压力的情况下,它们大多是良性的。良性克隆扩增可以补偿随着年龄增长而丧失的HSC再生能力。CHIP是一种衰老标志物,反映了HSC衰老与细胞外源性因素之间的生物学相互作用。CHIP的临床意义是高度可变的,取决于临床情况。区分调节克隆行为的因果关系和混杂因素对于确定CHIP在衰老中的机制作用并可能减轻其临床后果至关重要。
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引用次数: 16
Dynamic regulation of hematopoietic stem cells by bone marrow niches. 骨髓生态位对造血干细胞的动态调控。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-09-01 Epub Date: 2018-08-02 DOI: 10.1007/s40778-018-0132-x
Margot May, Anastasiya Slaughter, Daniel Lucas

Purpose of review: Hematopoietic stem cells (HSC) reside in a specialized microenvironment called the HSC niche. While key components of the niche have been known for several years, recent advances have identified several additional cell types that regulate HSC in the bone marrow (BM). Here we review our current understanding of the components and dynamics of the HSC niche.

Recent findings: While the niche has been considered a stable structure, recent advances clearly show that the niche is regulated in a dynamic manner to control HSC traffic and function. Moreover the niche can rapidly remodel in response to insults to the BM in a process controlled by positive and negative regulators.

Summary: Multiple niche cells have been shown to be dynamically regulated by systemic and local signals to influence how the niche controls HSC function. Elucidating how different components of the niche coordinate to orchestrate HSC behavior is essential to understand how the hematopoietic system adjusts blood cell production to the demands of the body.

综述目的:造血干细胞(HSC)存在于一个称为HSC生态位的特殊微环境中。虽然这个生态位的关键成分已经知道了几年,但最近的进展已经确定了几种调节骨髓中HSC的额外细胞类型(BM)。在这里,我们回顾了我们目前对HSC生态位的组成和动态的理解。最近的发现:虽然生态位被认为是一个稳定的结构,但最近的进展清楚地表明,生态位以一种动态的方式调节来控制HSC的流量和功能。此外,生态位可以在一个由正调节因子和负调节因子控制的过程中迅速重塑,以响应对BM的侮辱。摘要:多个生态位细胞受到系统和局部信号的动态调节,影响生态位如何控制HSC功能。阐明生态位的不同组成部分如何协调协调造血干细胞的行为,对于理解造血系统如何根据身体的需要调整血细胞生产是至关重要的。
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引用次数: 14
Gene Editing of Stem Cells to Model and Treat Disease 干细胞基因编辑模型和治疗疾病
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-07-17 DOI: 10.1007/s40778-018-0140-x
J. Hollywood, D. Sanz, A. Davidson, P. Harrison
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引用次数: 0
Regulation of Stem Cell Therapy Travel 干细胞治疗旅行的调控
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-07-14 DOI: 10.1007/s40778-018-0134-8
I. Glenn Cohen, Shelly Simana
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引用次数: 6
The Ethics of Chimera Creation in Stem Cell Research 干细胞研究中嵌合体产生的伦理问题
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-07-09 DOI: 10.1007/s40778-018-0136-6
I. Hyun
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引用次数: 10
Molecular Moirai: Long Noncoding RNA Mediators of HSC Fate. 分子生物学:长链非编码RNA介导HSC命运。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-06-01 Epub Date: 2018-04-16 DOI: 10.1007/s40778-018-0130-z
Nathaniel Magilnick, Mark P Boldin

Purpose of review: Hematopoiesis is an ordered developmental process that requires dynamic regulation to warrant proper response to physiological challenges and prevent malignancies. Long noncoding RNAs are emerging as key, multi-faceted regulators of gene expression. This review explores the function of lncRNAs in the control of HSC homeostasis and hematopoietic differentiation.

Recent findings: Multiple lncRNAs have been implicated in maintaining HSC stemness and enabling progenitors to carry out the correct programs of lineage differentiation. Specific lncRNAs have been identified that regulate the differentiation of multipotent progenitors into terminally differentiated blood cells. These lncRNAs predominantly act by assisting master regulators that drive specific differentiation programs, either by enhancing or repressing the transcription of particular genomic loci.

Summary: Long noncoding RNAs contribute to the correct differentiation and maturation of various hematopoietic lineages by assisting with the activation of transcriptional programs in a time- and cell-dependent manner.

综述目的:造血是一个有序的发育过程,需要动态调节以保证对生理挑战的适当反应和预防恶性肿瘤。长链非编码rna正成为基因表达的关键、多方面调控因子。本文就lncrna在控制HSC稳态和造血分化中的作用进行了综述。最近的研究发现:多个lncrna参与维持HSC的干细胞性,并使祖细胞能够执行正确的谱系分化程序。已经鉴定出特异性lncrna调节多能祖细胞向终分化血细胞的分化。这些lncrna主要通过增强或抑制特定基因组位点的转录来协助驱动特定分化程序的主调控因子。摘要:长链非编码rna通过以时间和细胞依赖的方式协助转录程序的激活,有助于各种造血谱系的正确分化和成熟。
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引用次数: 2
Maternal and Fetal Immune Response to in Utero Stem Cell Transplantation. 母体和胎儿对子宫内干细胞移植的免疫反应。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-06-01 Epub Date: 2018-05-03 DOI: 10.1007/s40778-018-0129-5
Amir Alhajjat, Aimen Shaaban

Purpose of review: In Utero Hematopoietic Cellular Transplantation (IUHCT) is a promising intervention for the non-toxic treatment of congenital disease that hinges on the assumption of fetal immunologic immaturity and an inability to reject a hematopoietic allograft. However, clinical IUCHT has failed except in cases where the fetus is severely immunocompromised. The current review examines recent studies of engraftment barriers stemming from either the fetal or maternal immune system.

Recent findings: New reports have illuminated roles for maternal humoral and cellular immunity and fetal innate cellular immunity in the resistance to allogeneic IUHCT. These experimental findings have inspired new approaches to overcome these barriers. Despite these advances, postulates regarding a maternal immune barrier to IUHCT provide an inadequate explanation for the well-documented clinical success only in the treatment of fetal immunodeficiency with normal maternal immunity.

Summary: Characterization of the maternal and fetal immune response to allogeneic IUHCT provides new insight into the complexity of prenatal tolerance. Future work in this area should aim to provide a unifying explanation for the observed patterns of success and failure with clinical IUHCT.

回顾目的:子宫内造血细胞移植(IUHCT)是一种很有前途的无毒性治疗先天性疾病的干预措施,这取决于胎儿免疫不成熟和无法排斥造血异体移植物的假设。然而,除了胎儿免疫功能严重受损的情况外,临床IUCHT失败了。目前的综述检查了来自胎儿或母体免疫系统的植入障碍的最新研究。最新发现:新的报告阐明了母体体液免疫和细胞免疫以及胎儿先天细胞免疫在抵抗异体IUHCT中的作用。这些实验发现激发了克服这些障碍的新方法。尽管取得了这些进展,但关于母体免疫屏障的假设并不能充分解释为什么只有在正常母体免疫治疗胎儿免疫缺陷方面取得了充分的临床成功。摘要:母体和胎儿对同种异体IUHCT免疫反应的表征为产前耐受的复杂性提供了新的见解。该领域未来的工作应旨在为临床IUHCT观察到的成功和失败模式提供统一的解释。
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引用次数: 2
It's Electric: When Technology Gives a Boost to Stem Cell Science. 它是电的:当技术推动干细胞科学。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-06-01 Epub Date: 2018-04-24 DOI: 10.1007/s40778-018-0124-x
Abraham P Lee, Mohammad Aghaamoo, Tayloria N G Adams, Lisa A Flanagan

Purpose of review: Advanced technologies can aid discoveries in stem cell science in surprising ways. The application of electrokinetic techniques, which use electric fields to interrogate or separate cells, to the study of stem cells has yielded important insights into stem cell function. These techniques probe inherent cell properties, obviating the need for cell-type specific labels.

Recent findings: Analysis of a variety of stem cell types including hematopoietic, mesenchymal and adipose-derived, neural, and pluripotent stem cells by electrokinetic techniques has revealed fate-specific signatures of cells. Distinct inherent cell properties are sufficient for their label-free enrichment without causing cell damage or toxicity.

Summary: The successful application of label-free techniques to the analysis and sorting of stem cells open new avenues for exploring the basic biology of stem cells and optimizing their use in regenerative medicine applications.

综述目的:先进的技术可以以令人惊讶的方式帮助干细胞科学的发现。利用电场审问或分离细胞的电动力学技术在干细胞研究中的应用已经对干细胞功能产生了重要的见解。这些技术探测固有的细胞特性,避免了对细胞类型特定标签的需要。最近发现:通过电动技术分析多种干细胞类型,包括造血干细胞、间充质干细胞和脂肪干细胞、神经干细胞和多能干细胞,揭示了细胞的命运特异性特征。独特的固有细胞特性足以使其无标记富集而不引起细胞损伤或毒性。摘要:无标记技术在干细胞分析和分选中的成功应用,为探索干细胞的基础生物学和优化其在再生医学中的应用开辟了新的途径。
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引用次数: 12
Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil. 干细胞调控中的缺氧信号通路:好与坏。
IF 1.4 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-06-01 Epub Date: 2018-04-30 DOI: 10.1007/s40778-018-0127-7
Xinxin Huang, Thao Trinh, Arafat Aljoufi, Hal E Broxmeyer

Purpose of review: This review summarizes the role of hypoxia and hypoxia-inducible factors (HIFs) in the regulation of stem cell biology, specifically focusing on maintenance, differentiation, and stress responses in the context of several stem cell systems. Stem cells for different lineages/tissues reside in distinct niches, and are exposed to diverse oxygen concentrations. Recent studies have revealed the importance of the hypoxia signaling pathway for stem cell functions.

Recent findings: Hypoxia and HIFs contribute to maintenance of embryonic stem cells, generation of induced pluripotent stem cells, functionality of hematopoietic stem cells, and survival of leukemia stem cells. Harvest and collection of mouse bone marrow and human cord blood cells in ambient air results in fewer hematopoietic stem cells recovered due to the phenomenon of Extra PHysiologic Oxygen Shock/Stress (EPHOSS).

Summary: Oxygen is an important factor in the stem cell microenvironment. Hypoxia signaling and HIFs play important roles in modeling cellular metabolism in both stem cells and niches to regulate stem cell biology, and represent an additional dimension that allows stem cells to maintain an undifferentiated status and multilineage differentiation potential.

综述目的:本文综述了缺氧和缺氧诱导因子(hif)在干细胞生物学调控中的作用,特别关注了几种干细胞系统的维持、分化和应激反应。不同谱系/组织的干细胞存在于不同的生态位中,并暴露于不同的氧浓度。最近的研究揭示了缺氧信号通路对干细胞功能的重要性。最近的研究发现:缺氧和hfs有助于胚胎干细胞的维持、诱导多能干细胞的产生、造血干细胞的功能和白血病干细胞的存活。在环境空气中采集小鼠骨髓和人脐带血细胞,由于额外生理性氧休克/应激(EPHOSS)现象,恢复的造血干细胞较少。摘要:氧是干细胞微环境中的一个重要因素。缺氧信号和hif在干细胞和小生境的细胞代谢建模中发挥重要作用,以调节干细胞生物学,并代表了允许干细胞保持未分化状态和多谱系分化潜力的额外维度。
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引用次数: 48
期刊
Current Stem Cell Reports
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