scholarly journals The NF-κB pathway regulates heterochromatin at intronic young LINE-1 elements and hematopoietic stem cell gene expression during irradiation stress

2021 ◽  
Author(s):  
Yanis Pelinski ◽  
Donia Hidaoui ◽  
Francois Hermetet ◽  
Anne Stolz ◽  
M'boyba Khadija Diop ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Regulatory Networks ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Cell Gene Expression ◽  
And Function

Understanding how ionizing radiations (IR) alter hematopoietic stem cell (HSC) function on the long-term is crucial. We recently showed a link between derepression of L1Md, the mouse young subfamilies of LINE-1/L1 retroelements, and IR-induced HSC injury. L1 contribute to gene regulatory networks. However, the mechanisms involved in IR-induced L1Md derepression, and their impact on HSC transcriptome remain to be addressed. Here we show that IR triggers genome-wide H3K9me3 decreased and transcriptomic changes in HSCs, characterized by a loss of the TNF-α/NF-κB and HSC signatures. HSC gene repression is associated to H3K9me3 loss at specific intronic L1Md displaying NF-κB binding sites. This is correlated with reduced NFKB1 repressor expression. TNF-α treatment before IR rescued all these effects and prevented IR-induced HSC loss of function in vivo. This reveals the importance of the TNF-α/NF-κB pathway to control H3K9me3 levels at selected intronic L1Md and thereby preserve HSC gene expression and function during IR stress.

scholarly journals Functional Analysis of Human Hematopoietic Stem Cell Gene Expression Using Zebrafish

PLoS Biology ◽  
2005 ◽  
Vol 3 (8) ◽  
pp. e254 ◽  
Author(s):  
Craig E Eckfeldt ◽  
Eric M Mendenhall ◽  
Catherine M Flynn ◽  
Tzu-Fei Wang ◽  
Michael A Pickart ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Stem Cell Gene

The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5121-5124 ◽  
Author(s):  
Thomas Bee ◽  
Emma L.K. Ashley ◽  
Sorrel R.B. Bickley ◽  
Andrew Jarratt ◽  
Pik-Shan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Reporter Gene ◽  
Specific Pattern ◽  
Reporter Gene Expression ◽  
Alternative Promoters ◽  
Specific Expression ◽  
Hematopoietic Stem

Abstract The transcription factor Runx1 plays a pivotal role in hematopoietic stem cell (HSC) emergence, and studies into its transcriptional regulation should give insight into the critical steps of HSC specification. Recently, we identified the Runx1 +23 enhancer that targets reporter gene expression to the first emerging HSCs of the mouse embryo when linked to the heterologous hsp68 promoter. Endogenous Runx1 is transcribed from 2 alternative promoters, P1 and P2. Here, we examined the in vivo cis-regulatory potential of these alternative promoters and asked whether they act with and contribute to the spatiotemporal specific expression of the Runx1 +23 enhancer. Our results firmly establish that, in contrast to zebrafish runx1, mouse Runx1 promoter sequences do not confer any hematopoietic specificity in transgenic embryos. Yet, both mouse promoters act with the +23 enhancer to drive reporter gene expression to sites of HSC emergence and colonization, in a +23-specific pattern.

scholarly journals Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence

2014 ◽  
Vol 211 (12) ◽  
pp. 2411-2423 ◽  
Author(s):  
Jordi Guiu ◽  
Dylan J.M. Bergen ◽  
Emma De Pater ◽  
Abul B.M.M.K. Islam ◽  
Verónica Ayllón ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
De Novo ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Hematopoietic Differentiation ◽  
Loss Of Function ◽  
Promoter Regions ◽  
Hematopoietic Stem

Hematopoietic stem cell (HSC) specification occurs in the embryonic aorta and requires Notch activation; however, most of the Notch-regulated elements controlling de novo HSC generation are still unknown. Here, we identify putative direct Notch targets in the aorta-gonad-mesonephros (AGM) embryonic tissue by chromatin precipitation using antibodies against the Notch partner RBPj. By ChIP-on-chip analysis of the precipitated DNA, we identified 701 promoter regions that were candidates to be regulated by Notch in the AGM. One of the most enriched regions corresponded to the Cdca7 gene, which was subsequently confirmed to recruit the RBPj factor but also Notch1 in AGM cells. We found that during embryonic hematopoietic development, expression of Cdca7 is restricted to the hematopoietic clusters of the aorta, and it is strongly up-regulated in the hemogenic population during human embryonic stem cell hematopoietic differentiation in a Notch-dependent manner. Down-regulation of Cdca7 mRNA in cultured AGM cells significantly induces hematopoietic differentiation and loss of the progenitor population. Finally, using loss-of-function experiments in zebrafish, we demonstrate that CDCA7 contributes to HSC emergence in vivo during embryonic development. Thus, our study identifies Cdca7 as an evolutionary conserved Notch target involved in HSC emergence.

scholarly journals 91. Retroviral Vector Integrations Relate to Hematopoietic Stem Cell Gene Expression Patterns

2006 ◽  
Vol 13 ◽  
pp. S37-S38
Author(s):  
Martijn H. Brugman ◽  
Karin Pike-Overzet ◽  
Carla Oerlemans- Bergs ◽  
Sigrid Swagemakers ◽  
Dick de Ridder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Expression Patterns ◽  
Retroviral Vector ◽  
Gene Expression Patterns ◽  
Hematopoietic Stem ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Stem Cell Gene

Nucleolin promotes execution of the hematopoietic stem cell gene expression program

Leukemia ◽  
2018 ◽  
Vol 32 (8) ◽  
pp. 1865-1868 ◽  
Author(s):  
Csaba Mahotka ◽  
Sanil Bhatia ◽  
Jutta Kollet ◽  
Edgar Grinstein
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Gene Expression Program ◽  
Hematopoietic Stem ◽  
Cell Gene Expression ◽  
Expression Program ◽  
Cell Gene ◽  
Stem Cell Gene

scholarly journals The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function

2015 ◽  
Vol 113 (1) ◽  
pp. E51-E60 ◽  
Author(s):  
Yue Gu ◽  
Amanda E. Jones ◽  
Wei Yang ◽  
Shanrun Liu ◽  
Qian Dai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Ubiquitin Ligase ◽  
Cell Function ◽  
Lymphoid Organ ◽  
Histone H2a ◽  
Hematopoietic Stem

Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitination (ubH2A) level and regulates hematopoiesis in vivo. Here we investigated the function of Usp16 in mouse hematopoiesis. Conditional deletion of Usp16 in bone marrow resulted in a significant increase of global ubH2A level and lethality. Usp16 deletion did not change HSC number but was associated with a dramatic reduction of mature and progenitor cell populations, revealing a role in governing HSC lineage commitment. ChIP- and RNA-sequencing studies in HSC and progenitor cells revealed that Usp16 bound to many important hematopoietic regulators and that Usp16 deletion altered the expression of genes in transcription/chromosome organization, immune response, hematopoietic/lymphoid organ development, and myeloid/leukocyte differentiation. The altered gene expression was partly rescued by knockdown of PRC1 subunits, suggesting that Usp16 and PRC1 counterbalance each other to regulate cellular ubH2A level and gene expression in the hematopoietic system. We further discovered that knocking down Cdkn1a (p21cip1), a Usp16 target and regulated gene, rescued the altered cell cycle profile and differentiation defect of Usp16-deleted HSCs. Collectively, these studies identified Usp16 as one of the histone H2A deubiquitinases, which coordinates with the H2A ubiquitin ligase PRC1 to regulate hematopoiesis, and revealed cell cycle regulation by Usp16 as key for HSC differentiation.

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.

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