scholarly journals CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells

Blood ◽  
2016 ◽  
Vol 128 (3) ◽  
pp. 371-383 ◽  
Author(s):  
Amy Sinclair ◽  
Laura Park ◽  
Mansi Shah ◽  
Mark Drotar ◽  
Simon Calaminus ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Murine Models ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Genetic Ablation ◽  
Key Points ◽  
Chemokine Ligands ◽  
Quiescent Hscs

Key Points Chemokine ligands CXCL1-4, 6, 10, 11, and 13 are upregulated in human quiescent HSCs with CXCR2 and CXCL4 regulating their survival. Genetic ablation of Cxcr2 or Cxcl4 in murine models induces initial expansion but eventual exhaustion of HSC in transplantation assays.

scholarly journals Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells

Blood ◽  
2017 ◽  
Vol 129 (13) ◽  
pp. 1779-1790 ◽  
Author(s):  
Hiroyoshi Kunimoto ◽  
Anna Sophia McKenney ◽  
Cem Meydan ◽  
Kaitlyn Shank ◽  
Abbas Nazir ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Progenitor Cells ◽  
Erythroid Differentiation ◽  
Genetic Loci ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Key Points

Key Points Aid loss leads to altered differentiation, transcription, and methylation in specific genetic loci in hematopoietic stem/progenitor cells. Aid loss does not contribute to enhanced HSC self-renewal or cooperate with Flt3-ITD in myeloid leukemogenesis.

scholarly journals Oncogenic N-Ras and Tet2 haploinsufficiency collaborate to dysregulate hematopoietic stem and progenitor cells

2018 ◽  
Vol 2 (11) ◽  
pp. 1259-1271 ◽  
Author(s):  
Xi Jin ◽  
Tingting Qin ◽  
Meiling Zhao ◽  
Nathanael Bailey ◽  
Lu Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progenitor Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Stem And Progenitor Cells

Key Points N-RasG12D and haploinsufficient Tet2 collaborate to induce lethal and highly penetrant CMML in mice with shortened overall survival. N-RasG12D and haploinsufficient Tet2 together promote balanced proliferation and enhanced competitiveness and self-renewal in HSPCs.

scholarly journals Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal

Blood ◽  
2021 ◽  
Author(s):  
Yuqing Yang ◽  
Andrew J Kueh ◽  
Zoe Grant ◽  
Waruni Abeysekera ◽  
Alexandra L Garnham ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Bone Marrow Cells ◽  
High Rate ◽  
Embryonic Patterning ◽  
Self Renewal ◽  
Hematopoietic Stem

The histone acetyltransferase HBO1 (MYST2, KAT7) is indispensable for postgastrulation development, histone H3 lysine 14 acetylation (H3K14Ac) and the expression of embryonic patterning genes. In this study, we report the role of HBO1 in regulating hematopoietic stem cell function in adult hematopoiesis. We used two complementary cre-recombinase transgenes to conditionally delete Hbo1 (Mx1-Cre and Rosa26-CreERT2). Hbo1 null mice became moribund due to hematopoietic failure with pancytopenia in the blood and bone marrow two to six weeks after Hbo1 deletion. Hbo1 deleted bone marrow cells failed to repopulate hemoablated recipients in competitive transplantation experiments. Hbo1 deletion caused a rapid loss of hematopoietic progenitors (HPCs). The numbers of lineage-restricted progenitors for the erythroid, myeloid, B-and T-cell lineages were reduced. Loss of HBO1 resulted in an abnormally high rate of recruitment of quiescent hematopoietic stem cells (HSCs) into the cell cycle. Cycling HSCs produced progenitors at the expense of self-renewal, which led to the exhaustion of the HSC pool. Mechanistically, genes important for HSC functions were downregulated in HSC-enriched cell populations after Hbo1 deletion, including genes essential for HSC quiescence and self-renewal, such as Mpl, Tek(Tie-2), Gfi1b, Egr1, Tal1(Scl), Gata2, Erg, Pbx1, Meis1 and Hox9, as well as genes important for multipotent progenitor cells and lineage-specific progenitor cells, such as Gata1. HBO1 was required for H3K14Ac through the genome and particularly at gene loci required for HSC quiescence and self-renewal. Our data indicate that HBO1 promotes the expression of a transcription factor network essential for HSC maintenance and self-renewal in adult hematopoiesis.

scholarly journals Mouse acute leukemia develops independent of self-renewal and differentiation potentials in hematopoietic stem and progenitor cells

2019 ◽  
Vol 3 (3) ◽  
pp. 419-431 ◽  
Author(s):  
Fang Dong ◽  
Haitao Bai ◽  
Xiaofang Wang ◽  
Shanshan Zhang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Leukemia ◽  
Progenitor Cells ◽  
Lymphoblastic Leukemia ◽  
The Self ◽  
Myelogenous Leukemia ◽  
Mouse Bone Marrow ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Abstract The cell of origin, defined as the normal cell in which the transformation event first occurs, is poorly identified in leukemia, despite its importance in understanding of leukemogenesis and improving leukemia therapy. Although hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were used for leukemia models, whether their self-renewal and differentiation potentials influence the initiation and development of leukemia is largely unknown. In this study, the self-renewal and differentiation potentials in 2 distinct types of HSCs (HSC1 [CD150+CD41−CD34−Lineage−Sca-1+c-Kit+ cells] and HSC2 [CD150−CD41−CD34−Lineage−Sca-1+c-Kit+ cells]) and 3 distinct types of HPCs (HPC1 [CD150+CD41+CD34−Lineage−Sca-1+c-Kit+ cells], HPC2 [CD150+CD41+CD34+Lineage−Sca-1+c-Kit+ cells], and HPC3 [CD150−CD41−CD34+Lineage−Sca-1+c-Kit+ cells]) were isolated from adult mouse bone marrow, and examined by competitive repopulation assay. Then, cells from each population were retrovirally transduced to initiate MLL-AF9 acute myelogenous leukemia (AML) and the intracellular domain of NOTCH-1 T-cell acute lymphoblastic leukemia (T-ALL). AML and T-ALL similarly developed from all HSC and HPC populations, suggesting multiple cellular origins of leukemia. New leukemic stem cells (LSCs) were also identified in these AML and T-ALL models. Notably, switching between immunophenotypical immature and mature LSCs was observed, suggesting that heterogeneous LSCs play a role in the expansion and maintenance of leukemia. Based on this mouse model study, we propose that acute leukemia arises from multiple cells of origin independent of the self-renewal and differentiation potentials in hematopoietic stem and progenitor cells and is amplified by LSC switchover.

scholarly journals Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells

Blood ◽  
2017 ◽  
Vol 130 (25) ◽  
pp. 2762-2773 ◽  
Author(s):  
Xin Zhao ◽  
Shouguo Gao ◽  
Zhijie Wu ◽  
Sachiko Kajigaya ◽  
Xingmin Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Cell ◽  
Progenitor Cells ◽  
Rna Seq ◽  
Hematopoietic Stem ◽  
Monosomy 7 ◽  
Key Points ◽  
Stem And Progenitor Cells ◽  
Diploid Cells ◽  
Transcriptome Signature

Key Points We distinguished aneuploid cells from diploid cells within the hematopoietic stem and progenitor cells using scRNA-seq. Monosomy 7 cells showed downregulated pathways involved in immune response and maintenance of DNA stability.

scholarly journals The control of hematopoietic stem cell maintenance, self-renewal, and differentiation by Mysm1-mediated epigenetic regulation

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2812-2822 ◽  
Author(s):  
Tao Wang ◽  
Vijayalakshmi Nandakumar ◽  
Xiao-Xia Jiang ◽  
Lindsey Jones ◽  
An-Gang Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Maintenance ◽  
Key Points ◽  
And Function ◽  
Cell Maintenance

Key Points Mysm1 is required to maintain the quiescence and pool size of HSC, and its deletion severely impairs the survival and function of HSC. Mysm1 controls HSC homeostasis by regulating Gfi1 expression via modulating histone modifications and transcriptional factors recruitment.

scholarly journals CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions

Cell Reports ◽  
2019 ◽  
Vol 26 (7) ◽  
pp. 1906-1918.e8 ◽  
Author(s):  
Johannes Jung ◽  
Sonja C. Buisman ◽  
Ellen Weersing ◽  
Albertina Dethmers-Ausema ◽  
Erik Zwart ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

scholarly journals Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2678-2688 ◽  
Author(s):  
Marisa Bowers ◽  
Bin Zhang ◽  
Yinwei Ho ◽  
Puneet Agarwal ◽  
Ching-Cheng Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem Cell ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Leukemia Development

Key Points Bone marrow OB ablation leads to reduced quiescence, long-term engraftment, and self-renewal capacity of hematopoietic stem cells. Significantly accelerated leukemia development and reduced survival are seen in transgenic BCR-ABL mice following OB ablation.

Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4369-4376 ◽  
Author(s):  
James C. Mulloy ◽  
Jorg Cammenga ◽  
Francisco J. Berguido ◽  
Kaida Wu ◽  
Ping Zhou ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Ex Vivo ◽  
Severe Combined Immunodeficiency ◽  
Hematopoietic Cells ◽  
The Self ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Human Cd34

AbstractHematopoiesis is a complex process involving hematopoietic stem cell (HSC) self-renewal and lineage commitment decisions that must continue throughout life. Establishing a reproducible technique that allows for the long-term ex vivo expansion of human HSCs and maintains self-renewal and multipotential differentiation will allow us to better understand these processes, and we report the ability of the leukemia-associated AML1-ETO fusion protein to establish such a system. AML1-ETO-transduced human CD34+ hematopoietic cells routinely proliferate in liquid culture for more than 7 months, remain cytokine dependent for survival and proliferation, and demonstrate self-renewal of immature cells that retain both lymphoid and myeloid potential in vitro. These cells continue to express the CD34 cell surface marker and have ongoing telomerase activity with maintenance of telomere ends, however they do not cause leukemia in nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. Identification of the signaling pathways that are modulated by AML1-ETO and lead to the self-renewal of immature human progenitor cells may assist in identifying compounds that can efficiently expand human stem and progenitor cells ex vivo. (Blood. 2003; 102:4369-4376)

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