scholarly journals Functional screen identifies regulators of murine hematopoietic stem cell repopulation

2016 ◽  
Vol 213 (3) ◽  
pp. 433-449 ◽  
Author(s):  
Per Holmfeldt ◽  
Miguel Ganuza ◽  
Himangi Marathe ◽  
Bing He ◽  
Trent Hall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Surface Receptor ◽  
The Novel ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Extracellular Matrix Components ◽  
Murine Hematopoietic Stem Cell ◽  
Surface Receptor ◽  
First Time

Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA-transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp521. Knockdown of each of these genes yielded a loss of function, except in the cases of Armcx1 and Gprasp2, whose loss enhanced hematopoietic stem cell (HSC) repopulation. The discovery of multiple genes regulating vesicular trafficking, cell surface receptor turnover, and secretion of extracellular matrix components suggests active cross talk between HSCs and the niche and that HSCs may actively condition the niche to promote engraftment. We validated that Foxa3 is required for HSC repopulating activity, as Foxa3−/− HSC fails to repopulate ablated hosts efficiently, implicating for the first time Foxa genes as regulators of HSPCs. We further show that Foxa3 likely regulates the HSC response to hematologic stress. Each gene discovered here offers a window into the novel processes that regulate stable HSPC engraftment into an ablated host.

scholarly journals Hematopoietic Stem Cell Transplantation Resolves the Immune Deficit Associated with STAT3-Dominant-Negative Hyper-IgE Syndrome

2021 ◽  
Author(s):  
Stephanie C. Harrison ◽  
Christo Tsilifis ◽  
Mary A. Slatter ◽  
Zohreh Nademi ◽  
Austen Worth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Early Report ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Hyper Ige Syndrome

AbstractAutosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor TH17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.

Discovery of the novel HLA‐C *06:195 allele in a Singaporean unrelated hematopoietic stem cell donor

HLA ◽  
2021 ◽  
Author(s):  
Louise Cho ◽  
Zi‐Jing Seng ◽  
Nezih Cereb ◽  
Py‐Yu Lin ◽  
Kuo‐Liang Yang
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
The Novel ◽  
Hematopoietic Stem ◽  
Cell Donor

scholarly journals MicroRNA-127-3p controls murine hematopoietic stem cell maintenance by limiting differentiation

Haematologica ◽  
2019 ◽  
Vol 104 (9) ◽  
pp. 1744-1755 ◽  
Author(s):  
Laura Crisafulli ◽  
Sharon Muggeo ◽  
Paolo Uva ◽  
Yulei Wang ◽  
Masayuki Iwasaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Maintenance ◽  
Murine Hematopoietic Stem Cell ◽  
Cell Maintenance

Characterization of the novel HLA‐DRB1*15:170 allele in a French hematopoietic stem cell donor

HLA ◽  
2020 ◽  
Vol 96 (3) ◽  
pp. 358-359 ◽  
Author(s):  
Céline Dard ◽  
Ornella Senoussi ◽  
Vincent Elsermans ◽  
Béatrice Bardy ◽  
Dominique Masson
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
The Novel ◽  
Hematopoietic Stem ◽  
Cell Donor

scholarly journals Pontin is essential for murine hematopoietic stem cell survival

Haematologica ◽  
2012 ◽  
Vol 97 (9) ◽  
pp. 1291-1294 ◽  
Author(s):  
O. Bereshchenko ◽  
E. Mancini ◽  
L. Luciani ◽  
A. Gambardella ◽  
C. Riccardi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Survival ◽  
Murine Hematopoietic Stem Cell

scholarly journals Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0158369 ◽  
Author(s):  
Alexandra Rundberg Nilsson ◽  
Shamit Soneji ◽  
Sofia Adolfsson ◽  
David Bryder ◽  
Cornelis Jan Pronk
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Aging ◽  
Functional Impairments ◽  
Hematopoietic Stem ◽  
Stem Cell Aging ◽  
Murine Hematopoietic Stem Cell

Long-term Residual Radiation Effect in the Murine Hematopoietic Stem Cell Compartment

1985 ◽  
Vol 459 (1 Hematopoietic) ◽  
pp. 221-231 ◽  
Author(s):  
K.-H. V. WANGENHEIM ◽  
H.P, PETERSON, ◽  
G. E. HÜBNER ◽  
L. E. FEINENDEGEN
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Radiation Effect ◽  
Cell Compartment ◽  
Hematopoietic Stem ◽  
Stem Cell Compartment ◽  
Murine Hematopoietic Stem Cell

Lnk Controls Hematopoietic Stem Cell Self-Renewal through Direct Interactions with JAK2 and Contributes to Oncogenic JAK2-Induced Myeloproliferative Diseases in Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 895-895
Author(s):  
Alexey Bersenev ◽  
Chao Wu ◽  
Joanna Balcerek ◽  
Wei Tong
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Hematopoietic Stem Cell ◽  
Adaptor Protein ◽  
Janus Kinase ◽  
Myelogenous Leukemia ◽  
Cell Surface Receptor ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Myeloproliferative Diseases

Abstract Hematopoietic stem cell (HSC) homeostasis and self-renewal are regulated by intrinsic cytokine signaling pathways. One important signaling axis for HSC is the cell surface receptor, Mpl, and its ligand, thrombopoietin (Tpo). Upon Tpo stimulation, Mpl activates Janus Kinase (JAK2) that triggers a cascade of downstream signal transduction pathways that regulates many aspects of cell development. Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk harbor an expanded HSC pool with enhanced self-renewal. Surprisingly, we found that Lnk−/− HSCs have an increased quiescent fraction, decelerated cell cycle kinetics, and enhanced resistance to repeated 5-Florouracil (5-FU) treatments in vivo compared to wild type HSCs. We further provided genetic evidence demonstrating that Lnk controls HSC quiescence and self-renewal predominantly through Mpl. Consistent with this observation, Lnk deficiency in HSCs potentiates JAK2 activation in response to TPO. Biochemical experiments reveal that Lnk directly binds to phosphorylated tyrosine residues in JAK2 following TPO stimulation. Dysregulation of cytokine receptor signaling pathways leads to hematological malignancies. Abnormal activation of JAK2 by a chromosomal translocation between the transcription factor Tel and JAK2 (Tel/JAK2) was shown to cause atypical Chronic Myelogenous Leukemia (aCML). Recently, the JAK2 V617F mutation has been observed at high frequencies in several myeloproliferative diseases (MPDs). The JAK2V617F mutant retains Lnk binding ability, suggesting Lnk status could modify MPD development. Indeed, we found that loss of Lnk accelerates oncogenic JAK2- induced CML/MPD in the mouse transplant models. Therefore, we identified Lnk as a physiological negative regulator of JAK2 in stem cells that may contribute to leukemic transformation conferred by oncogenic JAK2.

Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2231-2234 ◽  
Author(s):  
Daisuke Imanishi ◽  
Yasushi Miyazaki ◽  
Reishi Yamasaki ◽  
Yasushi Sawayama ◽  
Jun Taguchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Blood Cells ◽  
Hematopoietic Stem ◽  
Donor Cells ◽  
Cell Transplants ◽  
First Time ◽  
Hematopoietic Stem Cell Transplants ◽  
Short Tandem

To examine whether donor-derived cells could exist in nonhematopoietic tissues of recipients after allogeneic hematopoietic stem-cell transplantation, we examined the patterns of the short tandem repeat (STR) of DNA extracted from fingernail clippings of recipients so that the contamination of blood cells was excluded. All 21 patients reached donor-derived hematopoiesis after transplantation and 20 of them were in remission of the primary diseases at the time of sampling. Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from fingernail samples showed coexistence of the donor pattern of the STRs, sharing from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was from 305 to 2399 days among positive cases. These results demonstrate for the first time the existence of stable contribution of donor cells in fingernails among recipients of allogeneic hematopoietic stem cells.

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