Single‐cell analyses to reveal hematopoietic stem cell fate decisions

Lunger, Ilaria; Fawaz, Malak; Rieger, Michael A.

doi:10.1002/1873-3468.12712

Cited by 7 publications

(3 citation statements)

References 138 publications

(173 reference statements)

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“…Single-cell transcriptomic (scRNAseq) analysis unmasks heterogeneity and provides high-resolution mapping of highly complex systems including hematopoiesis (Lunger et al, 2017;Nam et al, 2019;Pellin et al, 2019). We previously reported that VPA-induced expression of CD90 and CD49f at single cell level (Papa et al, 2018).…”

Section: Vpa Treatment Induces Rapid and Robust Expression Of Hsc Phementioning

confidence: 99%

Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of ex vivo Expanded Human Hematopoietic Stem Cells

Papa

Djedaini

Martin

et al. 2020

Front. Cell Dev. Biol.

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Ex vivo expansion strategies of human hematopoietic stem cell (HSC) grafts with suboptimal stem cell dose have emerged as promising strategies for improving outcomes of HSC transplantation in patients with hematological malignancies. While exposure of HSCs to ex vivo cultures expands the number of phenotypically identifiable HSCs, it frequently alters the transcriptomic and metabolic profiles, therefore, compromising their long-term (LT) hematopoietic reconstitution capacity. Within the heterogeneous pool of expanded HSCs, the precise phenotypic, transcriptomic and metabolic profile and thus, the identity of HSCs that confer LT repopulation potential remains poorly described. Utilizing valproic acid (VPA) in ex vivo cultures of umbilical cord blood (UCB)-CD34+ cells, we demonstrate that expanded HSCs phenotypically marked by expression of the stem cell markers CD34, CD90 and EPCR (CD201) are highly enriched for LT-HSCs. Furthermore, we report that low mitochondrial membrane potential, and, hence, mitochondrial activity distinguishes LT-HSCs within the expanded pool of phenotypically defined HSCs. Remarkably, such reduced mitochondrial activity is restricted to cells with the highest expression levels of CD34, CD90 and EPCR phenotypic markers. Together, our findings reveal that high expression of CD34, CD90 and EPCR in conjunction with low mitochondrial activity is critical for identification of functional LT-HSCs generated within ex vivo expansion cultures.

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Section: Vpa Treatment Induces Rapid and Robust Expression Of Hsc Phementioning

confidence: 99%

Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of ex vivo Expanded Human Hematopoietic Stem Cells

Papa

Djedaini

Martin

et al. 2020

Front. Cell Dev. Biol.

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“…Previous studies have indicated that the heterogeneity of cellular states is caused by the cell physiology, differentiation state[4,5], and its inherent plasticity[6-8], hindering further studies of biological characteristics and applications of SCs[9]. Although bulk-based approaches using microarrays of high throughput RNA sequencing (RNAseq) techniques provide certain important insights into SCs, these approaches are limited because results about structures and functions reflect average measurements from large populations of cells or the results are predominantly obtained from cells with superior numbers[10,11], overlooking unique biological behaviors of individual cells, conceal cell-to-cell variations. As a consequence, heterogeneity is still a major issue to be resolved in the research and applications of SCs.…”

Section: Introductionmentioning

confidence: 99%

Applications of single cell RNA sequencing to research of stem cells

Zhang¹,

Liu²

2019

WJSC

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Stem cells (SCs) with their self-renewal and pluripotent differentiation potential, show great promise for therapeutic applications to some refractory diseases such as stroke, Parkinsonism, myocardial infarction, and diabetes. Furthermore, as seed cells in tissue engineering, SCs have been applied widely to tissue and organ regeneration. However, previous studies have shown that SCs are heterogeneous and consist of many cell subpopulations. Owing to this heterogeneity of cell states, gene expression is highly diverse between cells even within a single tissue, making precise identification and analysis of biological properties difficult, which hinders their further research and applications. Therefore, a defined understanding of the heterogeneity is a key to research of SCs. Traditional ensemble-based sequencing approaches, such as microarrays, reflect an average of expression levels across a large population, which overlook unique biological behaviors of individual cells, conceal cell-to-cell variations, and cannot understand the heterogeneity of SCs radically. The development of high throughput single cell RNA sequencing (scRNA-seq) has provided a new research tool in biology, ranging from identification of novel cell types and exploration of cell markers to the analysis of gene expression and predicating developmental trajectories. scRNA-seq has profoundly changed our understanding of a series of biological phenomena. Currently, it has been used in research of SCs in many fields, particularly for the research of heterogeneity and cell subpopulations in early embryonic development. In this review, we focus on the scRNA-seq technique and its applications to research of SCs.

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Section: Vpa Treatment Induces Rapid and Robust Expression Of Hsc Phementioning

confidence: 99%

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Single‐cell analyses to reveal hematopoietic stem cell fate decisions

Cited by 7 publications

References 138 publications

Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of ex vivo Expanded Human Hematopoietic Stem Cells

Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of ex vivo Expanded Human Hematopoietic Stem Cells

Applications of single cell RNA sequencing to research of stem cells

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