Imaging and spatial analysis of hematopoietic stem cell niches

Gomariz, Álvaro; Isringhausen, Stephan; Helbling, Patrick M.; Nombela‐Arrieta, César

doi:10.1111/nyas.14184

Cited by 21 publications

(30 citation statements)

References 67 publications

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“…3D-QM has been used by the group of Nombela-Arrieta to image the BM niche and its components ( 139 , 140 ), allowing the modeling of the entire bone surface. This approach has highlighted the real abundance and complex organization of the sinusoidal network and mesenchymal reticular subsets and its maintenance upon aging ( 141 ).…”

Section: Tools To Investigate the Aging Bm Nichementioning

confidence: 99%

Aging of the Hematopoietic Stem Cell Niche: New Tools to Answer an Old Question

2021

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The hematopoietic stem cell (HSC) niche is a specialized microenvironment, where a complex and dynamic network of interactions across multiple cell types regulates HSC function. During the last years, it became progressively clearer that changes in the HSC niche are responsible for specific alterations of HSC behavior. The aging of the bone marrow (BM) microenvironment has been shown to critically contribute to the decline in HSC function over time. Interestingly, while upon aging some niche structures within the BM are degenerated and negatively affect HSC functionality, other niche cells and specific signals are preserved and essential to retaining HSC function and regenerative capacity. These new findings on the role of the aging BM niche critically depend on the implementation of new technical tools, developed thanks to transdisciplinary approaches, which bring together different scientific fields. For example, the development of specific mouse models in addition to coculture systems, new 3D-imaging tools, ossicles, and ex-vivo BM mimicking systems is highlighting the importance of new technologies to unravel the complexity of the BM niche on aging. Of note, an exponential impact in the understanding of this biological system has been recently brought by single-cell sequencing techniques, spatial transcriptomics, and implementation of artificial intelligence and deep learning approaches to data analysis and integration. This review focuses on how the aging of the BM niche affects HSCs and on the new tools to investigate the specific alterations occurring in the BM upon aging. All these new advances in the understanding of the BM niche and its regulatory function on HSCs have the potential to lead to novel therapeutical approaches to preserve HSC function upon aging and disease.

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Section: Tools To Investigate the Aging Bm Nichementioning

confidence: 99%

Aging of the Hematopoietic Stem Cell Niche: New Tools to Answer an Old Question

2021

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“…Hematopoiesis in the bone marrow is spatially and regionally organized by specialized local microenvironments that support different types of stem cells and progenitors. The challenges in imaging the bone marrow tissue have limited progress ( 65 ). However, the future is bright.…”

Section: Discussionmentioning

confidence: 99%

Anatomy of Hematopoiesis and Local Microenvironments in the Bone Marrow. Where to?

Zhang

Lucas

2021

Front. Immunol.

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The shape and spatial organization -the anatomy- of a tissue profoundly influences its function. Knowledge of the anatomical relationships between parent and daughter cells is necessary to understand differentiation and how the crosstalk between the different cells in the tissue leads to physiological maintenance and pathological perturbations. Blood cell production takes place in the bone marrow through the progressive differentiation of stem cells and progenitors. These are maintained and regulated by a heterogeneous microenvironment composed of stromal and hematopoietic cells. While hematopoiesis has been studied in extraordinary detail through functional and multiomics approaches, much less is known about the spatial organization of blood production and how local cues from the microenvironment influence this anatomy. Here, we discuss some of the studies that revealed a complex anatomy of hematopoiesis where discrete local microenvironments spatially organize and regulate specific subsets of hematopoietic stem cells and/or progenitors. We focus on the open questions in the field and discuss how new tools and technological advances are poised to transform our understanding of the anatomy of hematopoiesis.

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“…The optimal site for HSC is the BM, that includes specialized areas called niches consisting of different cell types that control the number, quiescence, self-renewal, differentiation and distribution of HSCs ( 23 ). The niches are divided into two distinct, but equally connected areas: the first in which the osteoblast plays a primary role (Osteoblastic Niche); the second where endothelial cells predominate and has been called Vascular Niche ( 23 , 28 , 29 ).…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

et al. 2021

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The microenvironment that surrounds a tumor, in addition to the tumor itself, plays an important role in the onset of resistance to molecularly targeted therapies. Cancer cells and their microenvironment interact closely between them by means of a molecular communication that mutually influences their biological characteristics and behavior. Leukemia cells regulate the recruitment, activation and program of the cells of the surrounding microenvironment, including those of the immune system. Studies on the interactions between the bone marrow (BM) microenvironment and Acute Lymphoblastic Leukemia (ALL) cells have opened a scenario of potential therapeutic targets which include cytokines and their receptors, signal transduction networks, and hypoxia-related proteins. Hypoxia also enhances the formation of new blood vessels, and several studies show how angiogenesis could have a key role in the pathogenesis of ALL. Knowledge of the molecular mechanisms underlying tumor-microenvironment communication and angiogenesis could contribute to the early diagnosis of leukemia and to personalized molecular therapies. This article is part of a Special Issue entitled: Innovative Multi-Disciplinary Approaches for Precision Studies in Leukemia edited by Sandra Marmiroli (University of Modena and Reggio Emilia, Modena, Italy) and Xu Huang (University of Glasgow, Glasgow, United Kingdom).

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Imaging and spatial analysis of hematopoietic stem cell niches

Cited by 21 publications

References 67 publications

Aging of the Hematopoietic Stem Cell Niche: New Tools to Answer an Old Question

Aging of the Hematopoietic Stem Cell Niche: New Tools to Answer an Old Question

Anatomy of Hematopoiesis and Local Microenvironments in the Bone Marrow. Where to?

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

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