Novel Approaches in Hematopoiesis Research

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (30 January 2023) | Viewed by 24977

Special Issue Editors


E-Mail Website
Guest Editor
Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Interests: hematopoietic stem cells; cancer stem cells; neural stem cells

E-Mail Website
Guest Editor
Institute of Medical Science, University of Tokyo, Tokyo, Japan
Interests: hematopoietic stem cells; hematological malignancies; aging; epigenetics

Special Issue Information

Dear Colleagues,

Hematopoiesis, the process by which hematopoietic stem cells generate all blood cells, is the most extensively studied and characterized organogenesis event from the viewpoint of stem cells. Thus, one may think that the mechanisms that tightly regulate this multistep process have been well elucidated. However, in recent years, many innovative technological and conceptual developments have been implemented in the field of hematopoiesis research. For instance, single-cell transcriptome/metabolome analyses and gene editing have provided firm strategies for use in more in-depth studies of hematopoiesis. Significant progress has also been made in our understanding of aging and epigenetic memories that occur in hematopoietic stem cells. 

This Special Issue aims to summarize the latest approaches and current knowledge related to fundamental molecular and cellular mechanisms underlying hematopoiesis, with the hope of promoting further progress in hematopoiesis research. We encourage the submission of review articles, original research articles, short communications, or methodological articles dealing with various aspects of hematopoiesis, including, but not limited to, those exemplified above.

Dr. Tetsuya Taga
Prof. Dr. Atsushi Iwama
Guest Editors

Manuscript Submission Information

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Keywords

  • hematopoiesis
  • hematopoietic stem cells
  • aging
  • epigenetic memory
  • fetal hematopoiesis
  • gene therapy
  • gene editing
  • metabolome
  • transcriptome

Published Papers (5 papers)

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Review

34 pages, 1240 KiB  
Review
In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation
by Yavor K. Bozhilov, Ian Hsu, Elizabeth J. Brown and Adam C. Wilkinson
Cells 2023, 12(6), 896; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12060896 - 14 Mar 2023
Cited by 8 | Viewed by 8053
Abstract
The haematopoietic system plays an essential role in our health and survival. It is comprised of a range of mature blood and immune cell types, including oxygen-carrying erythrocytes, platelet-producing megakaryocytes and infection-fighting myeloid and lymphoid cells. Self-renewing multipotent haematopoietic stem cells (HSCs) and [...] Read more.
The haematopoietic system plays an essential role in our health and survival. It is comprised of a range of mature blood and immune cell types, including oxygen-carrying erythrocytes, platelet-producing megakaryocytes and infection-fighting myeloid and lymphoid cells. Self-renewing multipotent haematopoietic stem cells (HSCs) and a range of intermediate haematopoietic progenitor cell types differentiate into these mature cell types to continuously support haematopoietic system homeostasis throughout life. This process of haematopoiesis is tightly regulated in vivo and primarily takes place in the bone marrow. Over the years, a range of in vitro culture systems have been developed, either to expand haematopoietic stem and progenitor cells or to differentiate them into the various haematopoietic lineages, based on the use of recombinant cytokines, co-culture systems and/or small molecules. These approaches provide important tractable models to study human haematopoiesis in vitro. Additionally, haematopoietic cell culture systems are being developed and clinical tested as a source of cell products for transplantation and transfusion medicine. This review discusses the in vitro culture protocols for human HSC expansion and differentiation, and summarises the key factors involved in these biological processes. Full article
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)
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13 pages, 681 KiB  
Review
Approaches towards Elucidating the Metabolic Program of Hematopoietic Stem/Progenitor Cells
by Hiroshi Kobayashi, Shintaro Watanuki and Keiyo Takubo
Cells 2022, 11(20), 3189; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11203189 - 11 Oct 2022
Viewed by 1698
Abstract
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate [...] Read more.
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. Metabolites not only provide stem/progenitor cells with nutrients for ATP and building block generation but are also utilized for protein modification and epigenetic regulation to maintain cellular characteristics. In recent years, the metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods. In this review, we first present the advantages and disadvantages of the current approaches applicable to the metabolic analysis of tissue stem/progenitor cells, including HSCs and HPCs. In the second half, we discuss the characteristics and regulatory mechanisms of HSC metabolism, including the decoupling of ATP production by glycolysis and mitochondria. These technologies and findings have the potential to advance stem cell biology and engineering from a metabolic perspective and to establish therapeutic approaches. Full article
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)
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18 pages, 2033 KiB  
Review
Single Cell Transcriptomics to Understand HSC Heterogeneity and Its Evolution upon Aging
by Léonard Hérault, Mathilde Poplineau, Elisabeth Remy and Estelle Duprez
Cells 2022, 11(19), 3125; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11193125 - 4 Oct 2022
Cited by 2 | Viewed by 2772
Abstract
Single-cell transcriptomic technologies enable the uncovering and characterization of cellular heterogeneity and pave the way for studies aiming at understanding the origin and consequences of it. The hematopoietic system is in essence a very well adapted model system to benefit from this technological [...] Read more.
Single-cell transcriptomic technologies enable the uncovering and characterization of cellular heterogeneity and pave the way for studies aiming at understanding the origin and consequences of it. The hematopoietic system is in essence a very well adapted model system to benefit from this technological advance because it is characterized by different cellular states. Each cellular state, and its interconnection, may be defined by a specific location in the global transcriptional landscape sustained by a complex regulatory network. This transcriptomic signature is not fixed and evolved over time to give rise to less efficient hematopoietic stem cells (HSC), leading to a well-documented hematopoietic aging. Here, we review the advance of single-cell transcriptomic approaches for the understanding of HSC heterogeneity to grasp HSC deregulations upon aging. We also discuss the new bioinformatics tools developed for the analysis of the resulting large and complex datasets. Finally, since hematopoiesis is driven by fine-tuned and complex networks that must be interconnected to each other, we highlight how mathematical modeling is beneficial for doing such interconnection between multilayered information and to predict how HSC behave while aging. Full article
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)
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14 pages, 17352 KiB  
Review
Epigenetic Memories in Hematopoietic Stem and Progenitor Cells
by Kazumasa Aoyama, Naoki Itokawa, Motohiko Oshima and Atsushi Iwama
Cells 2022, 11(14), 2187; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11142187 - 13 Jul 2022
Cited by 6 | Viewed by 3053
Abstract
The recent development of next-generation sequencing (NGS) technologies has contributed to research into various biological processes. These novel NGS technologies have revealed the involvement of epigenetic memories in trained immunity, which are responses to transient stimulation and result in better responses to secondary [...] Read more.
The recent development of next-generation sequencing (NGS) technologies has contributed to research into various biological processes. These novel NGS technologies have revealed the involvement of epigenetic memories in trained immunity, which are responses to transient stimulation and result in better responses to secondary challenges. Not only innate system cells, such as macrophages, monocytes, and natural killer cells, but also bone marrow hematopoietic stem cells (HSCs) have been found to gain memories upon transient stimulation, leading to the enhancement of responses to secondary challenges. Various stimuli, including microbial infection, can induce the epigenetic reprogramming of innate immune cells and HSCs, which can result in an augmented response to secondary stimulation. In this review, we introduce novel NGS technologies and their application to unraveling epigenetic memories that are key in trained immunity and summarize the recent findings in trained immunity. We also discuss our most recent finding regarding epigenetic memory in aged HSCs, which may be associated with the exposure of HSCs to aging-related stresses. Full article
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)
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31 pages, 1173 KiB  
Review
Hematopoietic Stem Cell Gene-Addition/Editing Therapy in Sickle Cell Disease
by Paula Germino-Watnick, Malikiya Hinds, Anh Le, Rebecca Chu, Xiong Liu and Naoya Uchida
Cells 2022, 11(11), 1843; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11111843 - 4 Jun 2022
Cited by 10 | Viewed by 8681
Abstract
Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and β-thalassemia. SCD is caused by a point mutation (20A > T) in the β-globin gene. Since SCD is the most common single-gene [...] Read more.
Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and β-thalassemia. SCD is caused by a point mutation (20A > T) in the β-globin gene. Since SCD is the most common single-gene disorder, curing SCD is a primary goal in HSC gene therapy. β-thalassemia results from either the absence or the reduction of β-globin expression, and it can be cured using similar strategies. In HSC gene-addition therapy, patient CD34+ HSCs are genetically modified by adding a therapeutic β-globin gene with lentiviral transduction, followed by autologous transplantation. Alternatively, novel gene-editing therapies allow for the correction of the mutated β-globin gene, instead of addition. Furthermore, these diseases can be cured by γ-globin induction based on gene addition/editing in HSCs. In this review, we discuss HSC-targeted gene therapy in SCD with gene addition as well as gene editing. Full article
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)
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