Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment
César Nombela-Arrieta,Gregory Pivarnik,Beatrice Winkel,Kimberly J. Canty,Brendan A.C. Harley,John E. Mahoney,Shin-Young Park,Jiayun Lu,Alexei Protopopov,Alexei Protopopov,Leslie E. Silberstein +10 more
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TLDR
In situ tissue analysis reveals that HSPCs exhibit a hypoxic profile, defined by strong retention of pimonidazole and expression of HIF- 1α, regardless of localization throughout the bone marrow, adjacency to vascular structures or cell-cycle status.Abstract:
The existence of a haematopoietic stem cell niche as a spatially confined regulatory entity relies on the notion that haematopoietic stem and progenitor cells (HSPCs) are strategically positioned in unique bone marrow microenvironments with defined anatomical and functional features. Here, we employ a powerful imaging cytometry platform to perform a comprehensive quantitative analysis of HSPC distribution in bone marrow cavities of femoral bones. We find that HSPCs preferentially localize in endosteal zones, where most closely interact with sinusoidal and non-sinusoidal bone marrow microvessels, which form a distinctive circulatory system. In situ tissue analysis reveals that HSPCs exhibit a hypoxic profile, defined by strong retention of pimonidazole and expression of HIF-1α, regardless of localization throughout the bone marrow, adjacency to vascular structures or cell-cycle status. These studies argue that the characteristic hypoxic state of HSPCs is not solely the result of a minimally oxygenated niche but may be partially regulated by cell-specific mechanisms.read more
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Journal ArticleDOI
The bone marrow niche for haematopoietic stem cells
TL;DR: The haematopoietic stem cell niche remains incompletely defined and beset by competing models, and outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
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Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
TL;DR: In this paper, the authors identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties, which mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis.
Journal ArticleDOI
Arteriolar niches maintain haematopoietic stem cell quiescence
Yuya Kunisaki,Ingmar Bruns,Ingmar Bruns,Christoph Scheiermann,Christoph Scheiermann,Jalal Ahmed,Jalal Ahmed,Sandra Pinho,Dachuan Zhang,Toshihide Mizoguchi,Qiaozhi Wei,Daniel Lucas,Keisuke Ito,Jessica C. Mar,Aviv Bergman,Paul S. Frenette +15 more
TL;DR: It is shown that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow, indicating that arteriolar niches are indispensable for maintaining HSC quiescence.
Journal ArticleDOI
Direct measurement of local oxygen concentration in the bone marrow of live animals
Joel A. Spencer,Francesca Ferraro,Emmanuel Roussakis,Alyssa Klein,Juwell W. Wu,Judith Runnels,Walid Abbas Zaher,Luke J. Mortensen,Clemens Alt,Raphaël Turcotte,Rushdia Z. Yusuf,Daniel Côté,Sergei A. Vinogradov,David T. Scadden,Charles P. Lin +14 more
TL;DR: These pO2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.
Journal ArticleDOI
Metabolic requirements for the maintenance of self-renewing stem cells
Keisuke Ito,Toshio Suda +1 more
TL;DR: Investigation into the molecular mechanisms and metabolic pathways underlying stem cell self-renewal and differentiation hold great therapeutic promise.
References
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SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells
Mark J. Kiel,Ömer H. Yilmaz,Toshihide Iwashita,Osman H. Yilmaz,Cox Terhorst,Sean J. Morrison +5 more
TL;DR: This work compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoietic progenitors and found that both groups occupied multiple niches, including sinusoidal endothelium in diverse tissues.
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Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Simón Méndez-Ferrer,Tatyana V. Michurina,Francesca Ferraro,Amin R. Mazloom,Ben D. MacArthur,Ben D. MacArthur,Sergio A. Lira,David T. Scadden,Avi Ma'ayan,Grigori Enikolopov,Paul S. Frenette,Paul S. Frenette +11 more
TL;DR: It is demonstrated that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.
Journal ArticleDOI
Identification of the haematopoietic stem cell niche and control of the niche size
Jiwang Zhang,Chao Niu,Ling Ye,Haiyang Huang,Xi C. He,Wei Gang Tong,Jason Ross,Jeffrey S. Haug,Teri Johnson,Jian Q. Feng,Stephen E. Harris,Leanne M. Wiedemann,Leanne M. Wiedemann,Yuji Mishina,Linheng Li,Linheng Li +15 more
TL;DR: It is concluded that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of H SCs by regulating niche size.
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Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches
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