Studying hematopoiesis using single-cell technologies

Ye, Fang; Huang, Wentao; Guo, Guoji

doi:10.1186/s13045-017-0401-7

Cited by 53 publications

(41 citation statements)

References 121 publications

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“…Single-cell RNA sequencing has become a powerful tool to characterize distinct functional states at single-cell resolution [115][116][117]. Several studies using single-cell RNA sequencing have been performed to reveal cellintrinsic differences during HSC aging [22,25].…”

Section: Single Cell Technologies For Hsc Aging Single-cell Rna Sequementioning

confidence: 99%

“…The development of single-cell epigenomic technologies has allowed the identification of DNA methylation, histone modifications, chromatin accessibility, and chromosome conformation at the single-cell level [117,124]. For example, single-cell chromatin immunoprecipitation sequencing and single-cell assays for transposaseaccessible chromatin using sequencing (scATAC-seq) have been applied to investigate histone modifications and to map accessible chromatin regions.…”

Section: Epigenetics At the Single-cell Levelmentioning

confidence: 99%

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Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.

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Section: Single Cell Technologies For Hsc Aging Single-cell Rna Sequementioning

confidence: 99%

Section: Epigenetics At the Single-cell Levelmentioning

confidence: 99%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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“…Various hierarchical models for differentiation have been proposed (cf. Kawamoto, Wada, & Katsura, 2010;Ye, Huang, & Guo, 2017). The equal loss of potentials (ELP) model was introduced in Perié et al (2014), and is described next.…”

Section: Loss Of Potentials In Hematopoiesismentioning

confidence: 99%

On the role of the overall effect in exponential families

Klimová¹,

Rudas²

2018

Electron. J. Statist.

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Exponential families of discrete probability distributions when the normalizing constant (or overall effect) is added or removed are compared in this paper. The latter setup, in which the exponential family is curved, is particularly relevant when the sample space is an incomplete Cartesian product or when it is very large, so that the computational burden is significant. The lack or presence of the overall effect has a fundamental impact on the properties of the exponential family. When the overall effect is added, the family becomes the smallest regular exponential family containing the curved one. The procedure is related to the homogenization of an inhomogeneous variety discussed in algebraic geometry, of which a statistical interpretation is given as an augmentation of the sample space. The changes in the kernel basis representation when the overall effect is included or removed are derived. The geometry of maximum likelihood estimates, also allowing zero observed frequencies, is described with and without the overall effect, and various algorithms are compared. The importance of the results is illustrated by an example from cell biology, showing that routinely including the overall effect leads to estimates which are not in the model intended by the researchers.

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“…However, several studies have revealed novel concepts regarding HSC homeostasis that are distinct from the classical hierarchy 10 . Recent studies using transcriptomic, proteomic, and epigenetic profiling of HSCs have revealed that HSC populations are heterogeneous 11 , and studies with additional indicators have demonstrated that even the LT-HSC population is heterogeneous 12 . Therefore, additional tools are required to further separate HSCs into their component populations.…”

Section: Introductionmentioning

confidence: 99%

Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression

Ali

Fuse

Tadokoro

et al. 2017

Sci Rep

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1Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFP high cells exhibited significantly higher repopulating capacity than NS-GFP low cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFP high cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34 + cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.Hematopoietic stem cells (HSCs) perpetuate undifferentiated status through self-renewal, but also give rise to progenitors, which no longer possess the capacity for self-renewal but can differentiate into committed lineages 1 . Accumulating evidence supports the presence of "stemness" signals, that is, molecules and signaling pathways that play critical roles in maintaining the undifferentiated properties of HSCs. HSCs are maintained in a quiescent status in the bone marrow niches, and cooperative networks of intrinsic and extrinsic factors contribute to stem cell homeostasis in vivo 2 . To date, numerous factors involved in microenvironments, the cell cycle, metabolism, and epigenetics have been identified as regulators of HSC homeostasis 3, 4 ; however, it remains unclear how the stemness is regulated to maintain homeostasis.The identification of an HSC population is based on differential expression of cell surface markers. Positive selection for c-Kit (a receptor for stem cell factor; also known as CD117) and Sca-1 in combination with negative selection of mature hematopoietic markers (Lineage markers) efficiently enrich HSC/progenitor cells (Lineage − Sca-1 + c-Kit + ; LSK) 5 . Additional markers, including CD34, CD150, Flt3, and CD48, have been used to isolate HSCs that have long-term (LT) reconstitution activity (LT-HSCs, e.g. CD150− LSK cells) 6,7 .

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Studying hematopoiesis using single-cell technologies

Cited by 53 publications

References 121 publications

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

On the role of the overall effect in exponential families

Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression

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