scholarly journals Notchless-dependent ribosome synthesis is required for the maintenance of adult hematopoietic stem cells

2013 ◽  
Vol 210 (11) ◽  
pp. 2351-2369 ◽  
Author(s):  
Marie Le Bouteiller ◽  
Céline Souilhol ◽  
Sarah Beck-Cormier ◽  
Aline Stedman ◽  
Odile Burlen-Defranoux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Ribosome Biogenesis ◽  
Essential Role ◽  
Critical Factor ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Differentiated Cells ◽  
P53 Activation

Blood cell production relies on the coordinated activities of hematopoietic stem cells (HSCs) and multipotent and lineage-restricted progenitors. Here, we identify Notchless (Nle) as a critical factor for HSC maintenance under both homeostatic and cytopenic conditions. Nle deficiency leads to a rapid and drastic exhaustion of HSCs and immature progenitors and failure to maintain quiescence in HSCs. In contrast, Nle is dispensable for cycling-restricted progenitors and differentiated cells. In yeast, Nle/Rsa4 is essential for ribosome biogenesis, and we show that its role in pre-60S subunit maturation has been conserved in the mouse. Despite its implication in this basal cellular process, Nle deletion affects ribosome biogenesis only in HSCs and immature progenitors. Ribosome biogenesis defects are accompanied by p53 activation, which causes their rapid exhaustion. Collectively, our findings establish an essential role for Nle in HSC and immature progenitor functions and uncover previously unsuspected differences in ribosome biogenesis that distinguish stem cells from restricted progenitor populations.

The relative quiescence of hematopoietic stem cells in nonhuman primates

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3061-3068 ◽  
Author(s):  
Nadim Mahmud ◽  
Steven M. Devine ◽  
Kevin P. Weller ◽  
Simrit Parmar ◽  
Cord Sturgeon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Steady State ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
Primate Model ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Biological Potential

Abstract Quiescence has been thought to be required for the retention of the full biological potential of pluripotent hematopoietic stem cells (PHSCs). This hypothesis has been challenged recently by the observation that all murine PHSCs cycle continuously and constantly contribute to steady-state blood cell production. It was asked whether these observations could be extrapolated to describe hematopoiesis in higher mammals. In this series of experiments, the replicative history of PHSCs was examined in baboons by continuously administering bromodeoxyuridine (BrdU) for more than 85 weeks. The results indicate that under steady-state conditions, PHSCs remain largely quiescent but do cycle, albeit at a far lower rate than previously reported for rodent PHSCs. BrdU-labeled cycling PHSCs and progenitor cells were shown to have an extensive proliferative capacity and to contribute to blood cell production for prolonged periods of time. The proportion of PHSCs entering cell cycle could, however, be rapidly increased by the in vivo administration of granulocyte-colony stimulating factor. These data indicate that during steady-state hematopoiesis, baboon PHSCs require prolonged periods of time to cycle and that the proportion of PHSCs in cycle is not fixed but can be altered by external stimuli. The relative quiescence of PHSCs observed in this nonhuman primate model, in contrast to murine PHSCs, might explain the current barriers to genetic modification and ex vivo expansion of human PHSCs.

1016 – REGULATION OF RIBOSOME BIOGENESIS IN HEMATOPOIETIC STEM CELLS

2020 ◽  
Vol 88 ◽  
pp. S22
Author(s):  
Wei Tong ◽  
Kaosheng Lv ◽  
Charles Aruljothi ◽  
Chujie Gong ◽  
Xu Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ribosome Biogenesis ◽  
Hematopoietic Stem

scholarly journals Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells

2016 ◽  
Vol 65 (1) ◽  
pp. 69-81 ◽  
Author(s):  
Geoffrey Brown ◽  
Aleksandra Marchwicka ◽  
Alan Cunningham ◽  
Kai-Michael Toellner ◽  
Ewa Marcinkowska
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Hematopoietic Stem Cells ◽  
Myeloid Cell ◽  
Retinoic Acid Receptors ◽  
Hematopoietic Stem ◽  
Cell Production

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingqing Wu ◽  
Jizhou Zhang ◽  
Daniel Lucas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Spatial Organization ◽  
Hematopoietic Stem ◽  
Daughter Cells ◽  
Open Questions ◽  
Complex Anatomy ◽  
Technological Advances

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.

scholarly journals Understanding the Journey of Human Hematopoietic Stem Cell Development

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Akhilesh Kumar ◽  
Saritha S. D’Souza ◽  
Abir S. Thakur
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Human Blood ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Hematopoietic Stem ◽  
Hematopoietic Development

Hematopoietic stem cells (HSCs) surface during embryogenesis leading to the genesis of the hematopoietic system, which is vital for immune function, homeostasis balance, and inflammatory responses in the human body. Hematopoiesis is the process of blood cell formation, which initiates from hematopoietic stem/progenitor cells (HSPCs) and is responsible for the generation of all adult blood cells. With their self-renewing and pluripotent properties, human pluripotent stem cells (hPSCs) provide an unprecedented opportunity to createin vitromodels of differentiation that will revolutionize our understanding of human development, especially of the human blood system. The utilization of hPSCs provides newfound approaches for studying the origins of human blood cell diseases and generating progenitor populations for cell-based treatments. Current shortages in our knowledge of adult HSCs and the molecular mechanisms that control hematopoietic development in physiological and pathological conditions can be resolved with better understanding of the regulatory networks involved in hematopoiesis, their impact on gene expression, and further enhance our ability to develop novel strategies of clinical importance. In this review, we delve into the recent advances in the understanding of the various cellular and molecular pathways that lead to blood development from hPSCs and examine the current knowledge of human hematopoietic development. We also review howin vitrodifferentiation of hPSCs can undergo hematopoietic transition and specification, including major subtypes, and consider techniques and protocols that facilitate the generation of hematopoietic stem cells.

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