Hierarchy of Sca-1positive and Sca-1negative hematopoietic stem and progenitor cells and their contribution to blood cell production

2017 ◽  
Vol 53 ◽  
pp. S72
Author(s):  
Petr Paral ◽  
Katerina Faltusova ◽  
Martin Molik ◽  
Nicol Renesova ◽  
Ludek Sefc ◽  
...  
Keyword(s):  
Blood Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Stem And Progenitor Cells

Clonal Features of Hematopoietic Stem and Progenitor Cells in Aging

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 243-243
Author(s):  
Jianlong Sun ◽  
Fernando D. Camargo
Keyword(s):  
Blood Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Cell Populations ◽  
Multilineage Differentiation ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Stem And Progenitor Cells

Abstract It is traditionally thought that Hematopoietic Stem Cells (HSCs) maintain blood homeostasis through long-term self-renewal and multilineage differentiation. This concept, however, is challenged by two recent studies in which the fundamental features of unperturbed hematopoiesis are evaluated by different approaches of lineage tracing. Both the kinetic analysis of HSC output by the Rodewald group and our clonal analysis with transposon barcoding suggest a dominant role of non-transplantable short-term HSCs and progenitors, but not the long-term HSCs, in driving native blood cell production. In addition, our longitudinal analysis of peripheral blood demonstrates extensive clonal succession in granulocyte production. These findings collectively suggest a distinct mechanism of native hematopoiesis that differs significantly from what has been learned in transplantation experiments. At the same time, they bring to light new questions regarding the ultimate fate of the progenitor population and the exact contribution of HSCs under normal physiological conditions. To address these questions, we examined clonal features of HSCs and progenitors in aged mice. Our results show a progressive reduction in clonal complexity and a concurrent increase in clonal stability when blood granulocytes are analyzed up to a hundred ten weeks after transposon barcoding. As time elapses, clonal overlapping between granulocytes and B cells become much more extensive, suggesting an increased tendency toward multilineage differentiation during aging. Analysis of stem and progenitor cells in bone marrow of aged mice reveals prevalent lineage output by multipotent progenitors (MPPs), whereas a lower fraction of HSC clones are found to produce mature progeny. While this overall pattern of differentiation is reminiscent of what has been observed in young and middle-aged animals, a two-fold increase in HSC clonal output was observed in these old mice, indicating their increased contribution to blood cell production. A comparison of clonal compositions in blood and marrow cell populations demonstrates an MPP origin of stable peripheral blood clones, and a smaller fraction of these clones can even be traced back to HSCs. These observations hence suggest extensive self-renewal and asymmetric cell division of these two cell populations in aging. Taken together, our results indicate that the aged hematopoietic system is characterized by reduced clonal complexity, increased clonal persistence, and HSC activation. The higher propensity to self-renewal during aging may also explain the elevated risk of malignant transformation in the elderly population. Disclosures Camargo: Cell Signaling Technologies: Consultancy; Vital Therapies: Consultancy.

scholarly journals Hematopoiesis Remains Permissive to Bone Marrow Transplantation After Expansion of Progenitors and Resumption of Blood Cell Production

2021 ◽  
Vol 9 ◽  
Author(s):  
Martin Báječný ◽  
Chia-Ling Chen ◽  
Kateřina Faltusová ◽  
Tomáš Heizer ◽  
Katarína Szikszai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Cell ◽  
Progenitor Cells ◽  
Hematopoietic Cells ◽  
B Lymphopoiesis ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Virtual Absence ◽  
Myeloid Progenitors

The immense regenerative power of hematopoietic tissue stems from the activation of the immature stem cells and the progenitor cells. After partial damage, hematopoiesis is reconstituted through a period of intense regeneration when blood cell production originates from erythro-myeloid progenitors in the virtual absence of stem cells. Since the damaged hematopoiesis can also be reconstituted from transplanted hematopoietic cells, we asked whether this also leads to the transient state when activated progenitors initially execute blood cell production. We first showed that the early reconstitution of hematopoiesis from transplanted cells gives rise to extended populations of developmentally advanced but altered progenitor cells, similar to those previously identified in the bone marrow regenerating from endogenous cells. We then identified the cells that give rise to these progenitors after transplantation as LSK CD48– cells. In the submyeloablative irradiated host mice, the transplanted LSK CD48– cells preferably colonized the spleen. Unlike the endogenous hematopoiesis reconstituting cells, the transplanted whole bone marrow cells and sorted LSK CD48– cells had greater potential to differentiate to B-lymphopoiesis. Separate transplantation of the CD150– and CD150+ subsets of LSK CD48– cells suggested that CD150– cells had a greater preference to B-lymphopoiesis than CD150+ cells. In the intensively regenerating hematopoiesis, the CD71/Sca-1 plot of immature murine hematopoietic cells revealed that the expanded populations of altered myeloid progenitors were highly variable in the different places of hematopoietic tissues. This high variability is likely caused by the heterogeneity of the hematopoiesis supporting stroma. Lastly, we demonstrate that during the period when active hematopoiesis resumes from transplanted cells, the hematopoietic tissues still remain highly permissive for further engraftment of transplanted cells, particularly the stem cells. Thus, these results provide a rationale for the transplantation of the hematopoietic stem cells in successive doses that could be used to boost the transplantation outcome.

scholarly journals Megakaryocyte TGFβ1 Partitions Hematopoiesis into Immature Progenitor/Stem Cells and Maturing Precursors

2019 ◽  
Author(s):  
Silvana Di Giandomenico ◽  
Pouneh Kermani ◽  
Nicole Molle ◽  
Maria Mia Yabut ◽  
Ghaith Abu Zeinah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Progenitor Cells ◽  
Peripheral Blood Cell ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Erythroid Precursors ◽  
New Strategy ◽  
Stem And Progenitor Cells

SummaryErythropoiesis is a multiweek program coupling massive proliferation with progressive cellular differentiation ultimately enabling a limited number of hematopoietic stem cells (HSCs) to yield millions of erythrocytes per second1. Erythropoietin (Epo) is essential for red blood cell (RBC) production but this cytokine acts well after irreversible commitment of hematopoietic progenitor cells (HPCs) to an erythroid fate. It is not known if terminal erythropoiesis is tethered to the pool of available immature hematopoietic stem and progenitor cells (HSPCs). We now report that megakaryocyte-derived TGFβ1 compartmentalizes hematopoiesis by coupling HPC numbers to production of mature erythrocytes. Genetic deletion of TGFβ1 specifically in megakaryocytes (TGFβ1ΔMk/ΔMk) increased functional HSPCs including committed erythroid progenitors, yet total bone marrow and spleen cellularity and peripheral blood cell counts were entirely normal. Instead, excess erythroid precursors underwent apoptosis, predominantly those erythroblasts expressing the Epo receptor (Epor) but not Kit. Despite there being no deficiency of plasma Epo inTGFβ1ΔMk/ΔMkmice, exogenous Epo rescued survival of excess erythroid precursors and triggered exuberant erythropoiesis. In contrast, exogenous TGFβ1 caused anemia and failed to rescue erythroid apoptosis despite its ability to restore downstream TGFβ-mediated Smad2/3 phosphorylation in HSPCs. Thus, megakaryocytic TGFβ1 regulates the size of the pool of immature HSPCs and in so doing, improves the efficiency of erythropoiesis by governing the feed of lineage-committed erythroid progenitors whose fate is decided by extramedullary renal Epo-producing cells sensing the need for new RBCs. Independent manipulation of distinct immature Epo-unresponsive HSPCs within the hematopoietic compartments offers a new strategy to overcome chronic anemias or possibly other cytopenias.

scholarly journals Phenotypical Changes of Hematopoietic Stem and Progenitor Cells in Sepsis Patients: Correlation With Immune Status?

2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Wang ◽  
Jun Wang ◽  
Yi-hao Li ◽  
Lan Wang ◽  
Hong-cai Shang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
Blood Cell ◽  
Progenitor Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Healthy Control ◽  
Kinetics Of

Background: Sepsis is life-threatening organ dysfunction associated with high risk of death. The immune response of sepsis is complex and varies over time. The immune cells are derived from hematopoietic stem and progenitor cells (HSPCs) which can respond to many infections. Our previous study found that sepsis causes HSPC dysregulation in mouse. But few studies have previously investigated the kinetics of HSPC and its contribution to immune system in sepsis patients.Purpose: We aimed to identify the kinetics of HSPCs and their contribution to immune system in sepsis patients.Methods: We enrolled eight sepsis patients and five healthy control subjects. Peripheral blood (PB) samples from each patient were collected three times: on the first, fourth, and seventh days, once from each healthy control subject. Peripheral blood mononuclear cells (PBMCs) were isolated by density centrifugation and stained with cocktails of antibodies. Populations of HSPCs and their subpopulation were analyzed by flow cytometry. Immune cells were characterized by flow cytometry and blood cell analysis. Correlations between HSPCs and immune cells were analyzed using the Pearson correlation test.Results: We found that the frequency of HSPCs (CD34+ cells and CD34+CD38+ cells) in sepsis patients on day 4 was significantly higher than that in the healthy controls. The most pronounced change in subpopulation analysis is the frequency of common myeloid progenitors (CMPs; CD34+CD38+CD135+CD45RA−). But no difference in the immunophenotypically defined hematopoietic stem cells (HSCs; CD34+CD38−CD90+CD45RA−) in sepsis patients was observed due to rare HSC numbers in PB. The number of PBMCs and lymphocytes are decreased, whereas the white blood cell (WBC) and neutrophil counts were increased in sepsis patients. Importantly, we found a negative correlation between CD34+ on day 1 and WBC and lymphocytes on day 4 from correlation analysis in sepsis patients.Conclusion: The present study demonstrated that the HSPC and its subpopulation in sepsis patients expanded. Importantly, the changes in HSPCs at early time points in sepsis patients have negative correlations with later immune cells. Our results may provide a novel diagnostic indicator and a new therapeutic approach.

Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells

2001 ◽  
Vol 38 (2) ◽  
pp. 139-147
Author(s):  
Jan W. Gratama ◽  
D. Robert Sutherland ◽  
Michael Keeney
Keyword(s):  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Flow Cytometric ◽  
Stem And Progenitor Cells
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