Differentiated Cells Derived from Hematopoietic Stem Cells and Their Applications in Translational Medicine

2021 ◽  
pp. 29-43
Author(s):  
Sophia S. Fernandes ◽  
Lalita S. Limaye ◽  
Vaijayanti P. Kale
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Translational Medicine ◽  
Hematopoietic Stem ◽  
Differentiated Cells

Evidence that the number of hematopoietic stem cells per animal is conserved in mammals

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2665-2667 ◽  
Author(s):  
Janis L. Abkowitz ◽  
Sandra N. Catlin ◽  
Monica T. McCallie ◽  
Peter Guttorp
Keyword(s):  
Stem Cells ◽  
Life Expectancy ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Computational Approach ◽  
Evolutionary Adaptation ◽  
Hematopoietic Stem ◽  
Differentiated Cells ◽  
Human Hscs ◽  
Marrow Cells

Humans and larger mammals require more blood cells per lifetime than mice because of their larger size and longer life expectancy. To investigate this evolutionary adaptation, we calculated the total number of nucleated marrow cells (NMCs) per cat, observing the distribution of 59Fe to marrow, then multiplied this value (1.9 ± 0.9 × 1010 [mean ± SD]) times the frequency of feline hematopoietic stem cells (HSCs) (6 HSCs/107 NMCs) to derive the total number of HSCs per cat (11 400 ± 5400). Surprisingly, when the total number of HSCs per mouse was calculated with a similar experimental and computational approach, the value was equivalent. These data imply that the output of differentiated cells per feline HSC must vastly exceed that of murine HSCs. Furthermore, if the total number of human HSCs were also equivalent to the total number of HSCs in cat and mouse, the frequency of human HSCs would be 0.7 to 1.5 HSCs/108 NMCs, a frequency that is 20-fold less than estimated by the NOD/SCID repopulating assay.

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.

scholarly journals Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xufei Du ◽  
Fei Li ◽  
Chao Zhang ◽  
Na Li ◽  
Huaqiong Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Hematopoietic Stem ◽  
Differentiated Cells ◽  
Asthma Patients ◽  
Chemokine Ligand ◽  
Ccr1 Antagonist

AbstractEosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of eosinophils in asthmatic airway pathogenesis. However, their regulatory functions have not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described, which are mainly derived from eosinophils. Using Ccl6 knockout mice, further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin (OVA) challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells (HSCs). Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma.

PIG-A Mutations in Normal Hematopoiesis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2825-2825
Author(s):  
Rong Hu ◽  
Galina Mukhina ◽  
Steven Piantadosi ◽  
Richard J. Jones ◽  
Robert A. Brodsky
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Genetic Fidelity ◽  
Large Mammals ◽  
Hematopoietic Stem ◽  
Differentiated Cells ◽  
Mutational Frequency ◽  
Healthy Donors ◽  
Normal Individuals

Abstract Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by somatic mutations of the X-linked gene, PIG-A, in hematopoietic stem cells (HSCs). The product of this gene is necessary for the assembly of glycosylphosphatidylinositol (GPI) anchors. Consequently, PNH cells lack the expression of GPI-anchored proteins on their cell surface. PIG-A mutations have been found in granulocytes and T lymphocytes from most normal individuals. Although the significance of these mutations is unclear, it suggests that they are important in the pathogenesis of PNH. Methods: We isolated CD34+ progenitors from 4 PNH patients, 18 healthy donors, and 9 non-PNH patients undergoing peripheral blood stem cell tranplantation. The frequency of PIG-A mutant progenitors was determined by assaying for colony forming cells (CFC) in methylcellulose containing toxic doses of aerolysin. Aerolysin is a pore-forming toxin that uses the GPI anchor as it receptor; hence, PNH cells are unique in their resistance to aerolysin. DNA was extracted from individual day 14 aerolysin resistant CFC and the PIG-A gene was sequenced to determine clonality. We performed a Poisson distribution of the mutational frequency to determine the probability that the PIG-A mutation in controls arose from HSC. Results: In PNH patients, 67% of the CFC were aerolysin resistant. The frequency of aerolysin resistant CFC was 14.7 ± 4.0 x 10−6 in the bone marrow of healthy donors and was 57.0 ± 6.7 x 10−6 from mobilized peripheral blood. Aerolysin resistant CFC from PNH patients exhibited clonalPIG-A mutations, and thus, arose from HSC. In contrast, PIG-A mutations in the CFC from controls were polyclonal (up to 15 different mutations from one individual). Recent evidence suggests that humans and other large mammals possess only 10,000 primitive HSC, and that only 1000 of these cells are thought to contribute to hematopoiesis at any one time. Poisson statistics show that only 5% of normals would be expected to harbor a PIG-A mutation in 1000 HSC, and < 1 x 10−9 persons would harbor 10 or more different PIG-A mutations even if all 10,000 hematopoietic stem cells were contributing to hematopoiesis. Thus, the high frequency of PIG-A mutations in controls, coupled with their polyclonality, suggests that they do not arise at the level of HSC; rather, PIG-A mutations in normals appear to arise as a consequence of hematopoietic differentiation, between the level of an HSC and a CFC. Conclusion: Our data confirm the findings that PIG-A mutations are relatively common in normal hematopoiesis. Although we cannot rule out that a rare PIG-A mutant blood cell in normals does in fact arise from a mutant HSC, our data suggest that most of the mutations occur with differentiation. Genetic fidelity can be lost with differentiation without consequence, as mutations in differentiated cells would not be propagated. These data also call into question the relevance of PIG-A mutations in normals to the pathogenesis of PNH.

Cell staining for sorting of hematopoietic stem cells (HSC) and myeloid progenitors and isolating RNA from sorted cells

2006 ◽  
Author(s):  
Hideyo Hirai ◽  
Pu Zhang ◽  
Tajhal Dayaram ◽  
Christopher Hetherington ◽  
Shin-ichi Mizuno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Cell Staining ◽  
Myeloid Progenitors
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