scholarly journals Excessive fetal growth affects HSC quiescence maintenance through epigenetic programming of EGR1 transcriptional network

2021 ◽  
Author(s):  
Alexandre Pelletier ◽  
Arnaud Carrier ◽  
Yongmei Zhao ◽  
Mickael Canouil ◽  
Mehdi Derhourhi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Fetal Growth ◽  
Transcriptional Network ◽  
Large For Gestational Age ◽  
Dna Hypermethylation ◽  
Hematopoietic Stem ◽  
Maintenance Program ◽  
Epigenetic Programming

Fetal development is a critical period to shape stem cell identity and functions. Detrimental environments during this period are associated with epigenetics alteration of hematopoietic stem and progenitor cells (HSPC) with unknown functional impacts. We implemented a single-cell resolution integrative analysis combining epigenomics, transcriptomics, and functional data to elucidate the epigenetic influence associated with excessive fetal growth on HSPCs. We showed that hematopoietic stem cells (HSC) from large for gestational age neonates present a coordinated DNA hypermethylation and decrease expression for genes of the EGR1 transcriptional network including SOCS3, KLF2, and JUNB known to sustain stem cell quiescence and pluripotency. Furthermore, these changes were associated with a decreased ability for HSCs to stay undifferentiated and a decreased ability to expand in response to stimulation. Taken together, these results show that fetal overgrowth affects hematopoietic stem cells quiescence maintenance program through an epigenetic programming of the EGR1 related transcriptional network.

scholarly journals Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1.

1996 ◽  
Vol 183 (3) ◽  
pp. 1141-1150 ◽  
Author(s):  
C E Müller-Sieburg ◽  
R Riblet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Inbred Strains ◽  
Cell Number ◽  
Chromosome 1 ◽  
Cell Frequency ◽  
Candidate Locus ◽  
Hematopoietic Stem ◽  
Differentiation And Proliferation

The genetic elements that govern the differentiation and proliferation of hematopoietic stem cells remain to be defined. We describe here marked strain-specific differences in the frequency of long-term culture-initiating cells (LTC-IC) in the bone marrow of different strains of mice. Mice of C57Bl/6 background showed the lowest levels of stem cells in marrow, averaging 2.4 +/- .06 LTC-IC/10(5) cells, BALB/c is intermediate (9.1 +/- 4.2/10(5) cells), and DBA/2 mice contained a 11-fold higher frequency of LTC-IC (28.1 +/- 16.5/10(5) cells) than C57Bl/6 mice. The genetic factors affecting the size of the stem cell pool were analyzed in the C57Bl/6 X DBA/2 recombinant inbred strains; LTC-IC frequencies ranged widely, indicating that stem cell frequencies are controlled by multiple genes. Quantitative trait linkage analysis suggested that two loci that have major quantitative effects are located on chromosome 1 near Adprp and Acrg, respectively. The mapping of the locus near Adprp was confirmed by finding an elevated stem cell frequency in B6.C-H25, a C57Bl/6 congenic strain that carries a portion of chromosome 1 derived from BALB/c mice. We have named this gene Scfr1 (stem cell frequency regulator 1). The allelic forms of this gene may be an important predictor of stem cell number and thus would be useful for evaluating cell sources in clinical stem cell transplantation.

scholarly journals CD34+ Hematopoietic Stem Cells Exert Accessory Function in Lipopolysaccharide-induced  T Cell Stimulation and CD80 Expression on Monocytes

1999 ◽  
Vol 189 (4) ◽  
pp. 693-700 ◽  
Author(s):  
Taila Mattern ◽  
Gundolf Girroleit ◽  
Hans-Dieter Flad ◽  
Ernst T. Rietschel ◽  
Artur J. Ulmer
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cells ◽  
Cell Stimulation ◽  
Hematopoietic Stem ◽  
Accessory Function ◽  
T Cell Stimulation ◽  
Blood Stem Cells

CD34+ hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon γ production and proliferation. In contrast, stimulation of T cells by “conventional” recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34+ blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases.

Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells

Stem Cells ◽  
2018 ◽  
Vol 36 (8) ◽  
pp. 1237-1248
Author(s):  
Kateřina Faltusová ◽  
Katarína Szikszai ◽  
Martin Molík ◽  
Jana Linhartová ◽  
Petr Páral ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Green Fluorescent Protein ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Hematopoietic Stem ◽  
Green Fluorescent ◽  
Cell Defect

The Ethics of Embrionic Stem Cells Research

2019 ◽  
pp. 244-263
Author(s):  
Alexandra Huidu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Embryonic Stem Cell ◽  
Stem Cell Research ◽  
Embryonic Stem ◽  
Modern Medicine ◽  
Embryonic Stem Cell Research ◽  
Hematopoietic Stem ◽  
Research Fields

Embrionic stem cells research, as opposed to hematopoietic stem cells research, has always stirred up many controversies of ethical nature that have projected their effects in the specialized doctrine of the domain of medical bioethics and law. Some of these controversies have been transposed at the legislative level (both by international normative acts and by the national laws of the states) while others are not yet de object of consensus. All that is not transposed by law remains in the exclusive sphere of ethics, so the ethical discussion in embryonic stem cell research is not only relevant for today's modern medicine but also of the utmost importance for a category of specialists in various research fields.

scholarly journals Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo

2019 ◽  
Vol 116 (4) ◽  
pp. 1447-1456 ◽  
Author(s):  
Rong Lu ◽  
Agnieszka Czechowicz ◽  
Jun Seita ◽  
Du Jiang ◽  
Irving L. Weissman
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem Cell ◽  
Lineage Commitment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Different Levels

While the aggregate differentiation of the hematopoietic stem cell (HSC) population has been extensively studied, little is known about the lineage commitment process of individual HSC clones. Here, we provide lineage commitment maps of HSC clones under homeostasis and after perturbations of the endogenous hematopoietic system. Under homeostasis, all donor-derived HSC clones regenerate blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system has been perturbed by irradiation or by an antagonistic anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiate. Some of these clones dominantly expand and exhibit lineage bias. We identified the cellular origins of clonal dominance and lineage bias and uncovered the lineage commitment pathways that lead HSC clones to different levels of self-renewal and blood production under various transplantation conditions. This study reveals surprising alterations in HSC fate decisions directed by conditioning and identifies the key hematopoiesis stages that may be manipulated to control blood production and balance.

scholarly journals Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency

Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1622-1625 ◽  
Author(s):  
Serine Avagyan ◽  
Michael Churchill ◽  
Kenta Yamamoto ◽  
Jennifer L. Crowe ◽  
Chen Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem Cell ◽  
Premature Aging ◽  
Hematopoietic Stem ◽  
Cell Dysfunction ◽  
Key Points ◽  
Deficient Mice

Key Points XLF-deficient mice recapitulate the lymphocytopenia of XLF-deficient patients. Premature aging of hematopoietic stem cells underlies the severe and progressive lymphocytopenia in XLF-deficient mice.

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