scholarly journals Intravital Imaging Reveals Motility of Adult Hematopoietic Stem Cells in the Bone Marrow Niche

2020 ◽  
Vol 27 (2) ◽  
pp. 336-345.e4 ◽  
Author(s):  
Samik Upadhaya ◽  
Oleg Krichevsky ◽  
Ilseyar Akhmetzyanova ◽  
Catherine M. Sawai ◽  
David R. Fooksman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Intravital Imaging ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem

scholarly journals Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells

2016 ◽  
Vol 364 (3) ◽  
pp. 573-584 ◽  
Author(s):  
Patrick Wuchter ◽  
Rainer Saffrich ◽  
Stefan Giselbrecht ◽  
Cordula Nies ◽  
Hanna Lorig ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
In Vitro Model ◽  
Model System ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
In Vitro Model System ◽  
Vitro Model

Multimodal imaging reveals structural and functional heterogeneity in different bone marrow compartments: functional implications on hematopoietic stem cells

Blood ◽  
2013 ◽  
Vol 122 (10) ◽  
pp. 1730-1740 ◽  
Author(s):  
Francois Lassailly ◽  
Katie Foster ◽  
Lourdes Lopez-Onieva ◽  
Erin Currie ◽  
Dominique Bonnet
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Comparative Analysis ◽  
Hematopoietic Stem Cells ◽  
Multimodal Imaging ◽  
Intravital Imaging ◽  
Functional Heterogeneity ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Functional Implications

Key Points Comparative analysis of epiphyses, diaphyses, and calvaria in terms of homeostatic HSC content, homing, and early reconstitution is described. Noninvasive intravital imaging of intact bones and assessment of BVF, BRA, and hypoxia are reported.

scholarly journals Molecular Modulation of Fetal Liver Hematopoietic Stem Cell Mobilization into Fetal Bone Marrow in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Huihong Zeng ◽  
Jiaoqi Cheng ◽  
Ying Fan ◽  
Yingying Luan ◽  
Juan Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Vascular Endothelial Cells ◽  
Fetal Liver ◽  
Bone Marrow Niche ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Fetal Bone

Development of hematopoietic stem cells is a complex process, which has been extensively investigated. Hematopoietic stem cells (HSCs) in mouse fetal liver are highly expanded to prepare for mobilization of HSCs into the fetal bone marrow. It is not completely known how the fetal liver niche regulates HSC expansion without loss of self-renewal ability. We reviewed current progress about the effects of fetal liver niche, chemokine, cytokine, and signaling pathways on HSC self-renewal, proliferation, and expansion. We discussed the molecular regulations of fetal HSC expansion in mouse and zebrafish. It is also unknown how HSCs from the fetal liver mobilize, circulate, and reside into the fetal bone marrow niche. We reviewed how extrinsic and intrinsic factors regulate mobilization of fetal liver HSCs into the fetal bone marrow, which provides tools to improve HSC engraftment efficiency during HSC transplantation. Understanding the regulation of fetal liver HSC mobilization into the fetal bone marrow will help us to design proper clinical therapeutic protocol for disease treatment like leukemia during pregnancy. We prospect that fetal cells, including hepatocytes and endothelial and hematopoietic cells, might regulate fetal liver HSC expansion. Components from vascular endothelial cells and bones might also modulate the lodging of fetal liver HSCs into the bone marrow. The current review holds great potential to deeply understand the molecular regulations of HSCs in the fetal liver and bone marrow in mammals, which will be helpful to efficiently expand HSCs in vitro.

Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche

2012 ◽  
Vol 1266 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Fumio Arai ◽  
Kentaro Hosokawa ◽  
Hirofumi Toyama ◽  
Yoshiko Matsumoto ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem

In Vivo divisional Tracking System Reveals Cycling Heterogeneity in Long-Term Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 814-814
Author(s):  
Hitoshi Takizawa ◽  
Markus G Manz
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Model Systems ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Tracking Model

Abstract Abstract 814 Hematopoietic stem cells (HSCs) are defined by their capacity to self-renew and give rise to all mature cells of hemato-lymphoid system for the lifetime of an individual. To ensure this, HSCs are kept at homeostatic levels in adult bone marrow. Steady-state HSC cycling kinetics have been evaluated by in vivo labeling assay using 5-bromo-2-deoxyuridine (BrdU) (Cheshier et. al., PNAS 1999; Kiel et al., Nature 2007), biotin (Nygren et. al., PLoS ONE 2008) and histon 2B-green fluorescent protein (H2B-GFP) transgenic model systems (Wilson et. al., Cell 2008; Foudi et. al., Nat. Biotech. 2008). Based on the latter, it was suggested that one HSC pool turns over faster than another, dormant pool with very limited divisions during a lifetime. However, the fast cycling HSCs did not have long-term multilineage reconstitution capacity in lethally irradiated animals in contrast to dormant HSCs (Wilson et. al., Cell 2008; Foudi et.al., Nat. Biotech. 2008). From these experiments remained unclear, whether the faster cycling HSC loose long-term repopulation potential according to divisional history, or whether they represent progenitors with limited self-renewal potential, sharing a long-term HSC phenotype. Therefore, the dynamics of steady-state long-term HSC homeostasis and blood production remains to be determined. To address this directly, we set up an in vivo HSC divisional tracking assay. Here we show i.v. transfer of CFSE (carboxyfluorescein diacetate succinimidyl ester) -labeled HSCs into non-conditioned CD45.1/2 congenic F1 recipient mice that allows evaluation of steady-state HSC dynamics as CFSE distributes equally to daughter cells upon each cellular division. Sorted naïve CD4+CD62L+ T cells were used as non-dividing control cell population to determine the zero division CFSE staining level over time. Upon transfer of Lin-c-kit+Sca-1+ cells (LKS) into sublethally irradiated mice, all donor derived Lin-c-kit+ cells had divided >5 times after 3 weeks. However, transfer of LKS cells into non-irradiated mice revealed non-divided LKS cells in recipient bone marrow over 20 weeks. FACS analysis with HSC or progenitor specific marker expression showed that most of 0-2 time-divided and few of >5x divided LKS cells maintained a long-term HSC phenotype (CD150+, c-mpl+, CD34-). In order to test HSC potential, non- or >5x divided cells were sorted based on divisional history from primary recipients at different time points after transplantation, and competitively transplanted into lethally irradiated secondary recipients. At 3 weeks post primary transfer, single non-divided LKS cell was able to multi-lineage repopulate recipients, while 50 of >5x divided LKS cells showed no engraftment. Interestingly, both non- and >5x divided LKS cells at 7 or 12-14 weeks after primary transfer had long-term multilineage repopulating potential. Limiting dilution transplantation experiments demonstrated that HSC with long-term multilineage capacity (LT-HSC) were maintained at constant numbers that fit the numbers of free bone marrow niche space, with non-divided LT-HSC decreasing and >5x divided LT-HSC increasing with a constant division rate. We next tested the effects of hemato-immunological challenge on HSC cycling dynamics. Upon i.p. LPS injection into mice, previously transplanted with CFSE-labeled LKS, almost all LT-HSCs entered cell cycle within one week after challenge. These findings directly demonstrate that some LT-HSCs are quiescent for up to one fifth of the life-time of a mouse, while other LT-HSCs divide more actively, thus proving asynchronous LT-HSC division and contribution to hematopoiesis in steady-state. In addition, the results demonstrate that quiescent LT-HSCs are driven into division in response to naturally-occurring hematopoietic challenges, such as systemic bacterial infection. The CFSE-tracking model established here now allows to directly test the role of intrinsic versus environmental cues on cycling-dynamics of HSCs as well as leukemia initiating cells in steady-state and upon challenge on multiple genetic and different species background. Disclosures: No relevant conflicts of interest to declare.

scholarly journals ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells

2018 ◽  
Vol 11 (1) ◽  
pp. 258-273 ◽  
Author(s):  
Yu-feng Liu ◽  
Shao-ying Zhang ◽  
Ying-ying Chen ◽  
Kun Shi ◽  
Bin Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem

Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche

2012 ◽  
Vol 1266 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Kenichi Miharada ◽  
Göran Karlsson ◽  
Matilda Rehn ◽  
Emma Rörby ◽  
Kavitha Siva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem

scholarly journals Inflammation and Aging of Hematopoietic Stem Cells in Their Niche

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1849
Author(s):  
Daozheng Yang ◽  
Gerald de Haan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Niche ◽  
Extrinsic Factors ◽  
Hematopoietic Stem ◽  
Cell Lineages

Hematopoietic stem cells (HSCs) sustain the lifelong production of all blood cell lineages. The functioning of aged HSCs is impaired, including a declined repopulation capacity and myeloid and platelet-restricted differentiation. Both cell-intrinsic and microenvironmental extrinsic factors contribute to HSC aging. Recent studies highlight the emerging role of inflammation in contributing to HSC aging. In this review, we summarize the recent finding of age-associated changes of HSCs and the bone marrow niche in which they lodge, and discuss how inflammation may drive HSC aging.

scholarly journals Hematopoietic Stem Cells: Nature and Niche Nurture

2021 ◽  
Vol 8 (5) ◽  
pp. 67
Author(s):  
Geoffrey Brown
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
Cell Lineage ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Homogeneous Population ◽  
Starting Point ◽  
The Right

Like all cells, hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune cells. The starting point for engineering hematopoiesis ex vivo is the nature of HSCs, and a longstanding premise is that they are a homogeneous population of cells. However, recent findings have shown that adult bone marrow HSCs are really a mixture of cells, with many having lineage affiliations. A second key consideration is: Do HSCs “choose” a lineage in a random and cell-intrinsic manner, or are they instructed by cytokines? Since their discovery, the hematopoietic cytokines have been viewed as survival and proliferation factors for lineage committed HPCs. Some are now known to also instruct cell lineage choice. These fundamental changes to our understanding of hematopoiesis are important for placing niche support in the right context and for fabricating an ex vivo environment to support HSC development.

scholarly journals Innate Immune Signal-Regulated Hematopoiesis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-1-SCI-1
Author(s):  
Hitoshi Takizawa
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Innate Immune ◽  
Immune Memory ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Immune Reactions

Adult bone marrow (BM) had been long thought to be an immune-privileged organ where little immune reactions occur upon immunological challenges, and thus to form an advantageous environment to preserve long-lived hematopoietic and immune cells, e.g., hematopoietic stem cells (HSCs) that maintain lifelong hematopoiesis. They are mostly kept in quiescence, i.e., very slowly dividing within the steady state BM microenvironment, often referred to as niche, which consists of various type of non-hematopoietic cells such as endothelial cells, mesenchymal stromal cells1. In contrast, recent studies have suggested that a broad range of immunological and inflammatory responses occur in BM and largely influence HSC function2. Upon hematopoietic challenges, e.g., infection, inflammation, cancer, both HSCs and the surrounding niche cells can sense hematopoietic demand signals and integrate it to hematopoiesis via direct (HSC-mediated) and indirect (niche-mediated) sensing mechanisms. As a consequence, primitive HSC and their differentiated progenitors (HSPCs) migrate to inflamed organs, proliferate and differentiate into specific cell lineages that are locally consumed and to be replenished. Infection is one of hemato-immunological challenges that are highly conserved in evolution and relevant to pathogenesis of many diseases, e.g., cancer. Host defense against infection is initiated by rapid but relatively non-specific responses that involve innate immune effector cells, e.g., macrophages, granulocytes, and then is followed by slower but specific responses that involve acquired immunity. Recent studies have shown that not only immune cells but also HSPCs express innate immune sensors, such as Toll-like receptors (TLRs), and the ligation of receptors results in secretion of pro-inflammatory cytokines, cell migration, proliferation and differentiation into myeloid lineage cells (King, Nat Rev Immunol 2016). We have also shown that systemic infection of gram negative bacterial activates quiescent HSCs to proliferation through its cognate receptor, TLR4, and eventually impairs their hematopoietic repopulating ability3. More recently, we have found that intestinal tissue damage activates early hematopoiesis in BM via microbial signals and direct early HSPCs to inflamed lymph node to produce myeloid cells and promote tissue repair. Given the fact that innate immune cells are epigenetically programmed with innate immune memory upon sensitization ("training") infection to resist future infectious insults4, and that HSPCs are long-lived and immune-responsive, it has been demonstrated that upon exposure to pathogen, HSPCs also are able to memorize infection through metabolic and epigenetic changes, and build hemato-immune system with better protection to subsequent pathogen insults5. Taken together, these findings define the BM not as an immune-privileged reservoir, but rather as an organ of active immune reactions where immature HSPCs are capable of adapting the demand signal to hematopoiesis in response to hemato-immunological challenges, and of being trained by innate immune activation to reconstitute host defense with more resistance against future infection. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014 Jan 16;505(7483):327-34 Takizawa H, Boettcher S, Manz MG. Demand-adapted regulation of early hematopoiesis in infection and inflammation.Blood. 2012 Mar 29;119(13):2991-3002. Takizawa H, Fritsch K, Kovtonyuk LV, et al. Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness.Cell Stem Cell. 2017 Aug 3;21(2):225-240.e5. Netea MG, Joosten LA, Latz E, et al. Trained immunity: A program of innate immune memory in health and disease.Science. 2016 Apr 22;352(6284):aaf1098. Kopf M, Nielsen PJ. Training myeloid precursors with fungi, bacteria and chips. Nat Immunol. 2018 Apr;19(4):320-322. Disclosures No relevant conflicts of interest to declare.

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