scholarly journals Application of Fluid Mechanical Force to Embryonic Sources of Hemogenic Endothelium and Hematopoietic Stem Cells

2014 ◽  
pp. 183-193 ◽  
Author(s):  
Nan Li ◽  
Miguel F. Diaz ◽  
Pamela L. Wenzel
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mechanical Force ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem

scholarly journals The embryonic origins of hematopoietic stem cells: a tale of hemangioblast and hemogenic endothelium

Apmis ◽  
2005 ◽  
Vol 113 (11-12) ◽  
pp. 790-803 ◽  
Author(s):  
KARINE BOLLEROT ◽  
CLAIRE POUGET ◽  
THIERRY JAFFREDO
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem

scholarly journals Hematopoietic Stem Cells Develop in the Absence of Endothelial Cadherin 5 Expression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1165-1165
Author(s):  
Heidi Anderson ◽  
Taylor Patch ◽  
Pavan Reddy ◽  
Elliott Hagedorn ◽  
Owen J. Tamplin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Board Of Directors ◽  
Research Funding ◽  
Hemogenic Endothelium ◽  
Employment Equity ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Equity Ownership

Abstract Rare endothelial cells in the aorta-gonad-mesonephros (AGM) transition into hematopoietic stem cells (HSCs) during embryonic development. Lineage tracing experiments indicate that HSCs emerge from Cadherin 5 (Cdh5, VE-cadherin)+ endothelial precursors, and isolated populations of Cdh5+ cells from mouse embryos and embryonic stem (ES) cells can be differentiated into hematopoietic cells. Cdh5 has also been widely implicated as a marker of AGM-derived hemogenic endothelial cells. Since Cdh5-/- mice embryos die before the first HSCs emerge, it is unknown if Cdh5 has a direct role in HSC emergence. Our previous genetic screen yielded malbec (mlbbw306), a zebrafish mutant for cdh5, with normal embryonic and definitive blood. Utilizing time-lapse imaging, parabiotic surgical pairing of zebrafish embryos, and blastula transplantation assays, we show that HSCs emerge, migrate, engraft, and differentiate in the absence of cdh5 expression. By tracing Cdh5-/- GFP+/+ cells inchimeric mice, we demonstrated that Cdh5-/- GFP+/+ HSCs emerging from E10.5 and E11.5 AGM or derived from E13.5 fetal liver not only differentiate into hematopoietic colonies but also engraft and reconstitute multi-lineage adult blood. These data establish that Cdh5, a marker of hemogenic endothelium in the AGM, is dispensable for the transition of hemogenic endothelium to HSCs. Disclosures Bauer: Biogen: Research Funding; Editas Medicine: Consultancy. Zon:FATE Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder; Scholar Rock: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder. Orkin:Editas Medicine: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding; Pfizer: Research Funding; Sangamo Biosciences: Consultancy.

scholarly journals Transcriptional regulatory network controlling the ontogeny of hematopoietic stem cells

2019 ◽  
Author(s):  
Peng Gao ◽  
Changya Chen ◽  
Elizabeth D. Howell ◽  
Yan Li ◽  
Joanna Tober ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Hematopoietic Stem Cells ◽  
Developmental Stage ◽  
Regulatory Networks ◽  
Developmental Stages ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Transcriptional Regulatory ◽  
Computational Analyses

AbstractHematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-Seq and histone mark ChIP-Seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in the mouse. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries (dorsal aorta, umbilical and vitelline), an enriched population of pre-hematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. We observed dynamic and combinatorial epigenetic changes that mark regulatory DNA sequences including gene promoters and enhancers. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are established de novo at the developmental stages where they are required to control their target genes, without prior priming in earlier stages. We constructed developmental-stage-specific transcriptional regulatory networks during HSC ontogeny by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm. Our computational analyses predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors whose regulon activities correlate with the emergence of pre-HSCs. We validated roles for the broadly expressed transcription factors SP3 and MAZ in arterial hemogenic endothelium. Our data and computational analyses provide a useful resource for uncovering regulators of HSC formation.

scholarly journals Transforming Growth Factor β Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells

2016 ◽  
Vol 38 (4) ◽  
pp. 358-370 ◽  
Author(s):  
Rui Monteiro ◽  
Philip Pinheiro ◽  
Nicola Joseph ◽  
Tessa Peterkin ◽  
Jana Koth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem

Zebrafish Cbfb Is Required For The Mobilization, But Not The Emergence, Of Hematopoietic Stem Cells In Embryos

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 464-464
Author(s):  
Erica Bresciani ◽  
Blake Carrington ◽  
Stephen Wincovitch ◽  
Aniket Gore ◽  
Brant M. Weinstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Notch Pathway ◽  
Targeted Mutagenesis ◽  
Dorsal Aorta ◽  
Human Leukemia ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Definitive Hematopoiesis

CBFβ and RUNX1 form a DNA-binding heterodimer that plays a crucial role during definitive hematopoiesis at the stage of hematopoietic stem cells (HSCs). Both of them are targets of recurrent chromosomal translocations in human leukemia. In mammals and zebrafish, RUNX1 is required for the emergence of definitive HSCs from the hemogenic endothelium. Mouse knockouts for either Runx1 or Cbfb show similar phenotypes with complete lack of definitive hematopoiesis. Therefore, the impairment of all definitive hematopoietic lineages in both Runx1-/- and Cbfb-/- embryos suggested that the CBF heterodimer is required for HSC formation. However the exact role of the CBF complex in the development of HSCs remains unclear. The cellular mechanisms and the genetic pathways driving the HSC generation are highly conserved across vertebrates. Thus, we used the zebrafish model to dissect the role of cbfb and the CBF complex in the emergence and the maintenance of HSCs. We generated two independent cbfb knockouts (cbfb-/-) by zinc-finger nuclease (ZFN) - mediated targeted mutagenesis. The analysis of cbfb-/- embryos revealed a previously unknown role of cbfb during definitive hematopoiesis. Similar to the published zebrafish runx1 mutant embryos (runx1W84X/W84X), cbfb-/- embryos underwent primitive hematopoiesis and developed erythromyeloid progenitors (EMPs), but they lacked definitive hematopoiesis as the expression of markers for differentiated blood lineages such as rag1, lplastin and αe1globin was completely abrogated. Moreover, circulating thrombocytes were almost undetectable in cbfb-/-/tg(cd41:GFP) embryos. Unlike the runx1 mutants in which HSCs are not formed, however, the emergence of runx1+/c-myb+ HSCs from the hemogenic endothelium along the ventral wall of the dorsal aorta was unaffected in the cbfb-/- mutants. Rather, the subsequent translocation of the HSCs from aorta-gonad-mesonephros (AGM) to the caudal hematopoietic tissue (CHT) was blocked, as evidenced by the accumulation of runx1+ HSCs in the AGM and the concomitant absence of such cells in the CHT. Live imaging analysis of cbfb-/-/tg(c-myb:eGFP) embryos confirmed that HSCs egressed from the dorsal aorta but did not enter circulation through the axial vein. Moreover, embryos treated with a specific inhibitor of RUNX1-CBFβ interaction, Ro5-3335, phenocopied the hematopoietic defects observed in the cbfb-/- mutants, confirming that the function of RUNX1 and CBFβ during HSC development could be uncoupled. The Notch-Runx1 pathway is critical for the initial specification of HSCs during definitive hematopoiesis. Therefore, in order to gain insight into the genetic mechanisms that regulate cbfb expression we investigated the Notch pathway. We found that transient Notch activation enhanced cbfb expression and expanded it ectopically. On the other hand, in the Notch signaling mutant mind bomb, cbfb expression in hematopoietic regions was abrogated. Thus, our results suggest that cbfb is also downstream of the Notch pathway during hematopoiesis. Overall our data indicate that CBFβ and functional CBFβ-RUNX1 heterodimers are not required for the emergence of HSCs, but are essential for the mobilization of HSCs during early definitive hematopoiesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors

2019 ◽  
Vol 216 (7) ◽  
pp. 1599-1614 ◽  
Author(s):  
Tomomasa Yokomizo ◽  
Naoki Watanabe ◽  
Terumasa Umemoto ◽  
Junichi Matsuo ◽  
Ryota Harai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Fetal Liver ◽  
Hemogenic Endothelium ◽  
Developmental Pathway ◽  
Hematopoietic Stem ◽  
Reporter Mouse ◽  
Myeloid Progenitors

Before the emergence of hematopoietic stem cells (HSCs), lineage-restricted progenitors, such as erythro-myeloid progenitors (EMPs), are detected in the embryo or in pluripotent stem cell cultures in vitro. Although both HSCs and EMPs are derived from hemogenic endothelium, it remains unclear how and when these two developmental programs are segregated during ontogeny. Here, we show that hepatic leukemia factor (Hlf) expression specifically marks a developmental continuum between HSC precursors and HSCs. Using the Hlf-tdTomato reporter mouse, we found that Hlf is expressed in intra-aortic hematopoietic clusters and fetal liver HSCs. In contrast, EMPs and yolk sac hematopoietic clusters before embryonic day 9.5 do not express Hlf. HSC specification, regulated by the Evi-1/Hlf axis, is activated only within Hlf+ nascent hematopoietic clusters. These results strongly suggest that HSCs and EMPs are generated from distinct cohorts of hemogenic endothelium. Selective induction of the Hlf+ lineage pathway may lead to the in vitro generation of HSCs from pluripotent stem cells.

3063 – DISTINCT POPULATIONS OF MULTIPOTENT PROGENITORS AND HEMATOPOIETIC STEM CELLS EMERGE FROM HEMOGENIC ENDOTHELIUM IN THE MURINE EMBRYO

2020 ◽  
Vol 88 ◽  
pp. S57-S58
Author(s):  
Tessa Dignum ◽  
Barbara Varnum-Finney ◽  
Sanjay Srivatsan ◽  
Stacey Dozono ◽  
Olivia Waltner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
Murine Embryo

scholarly journals Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo

Cell Reports ◽  
2021 ◽  
Vol 36 (11) ◽  
pp. 109675
Author(s):  
Tessa Dignum ◽  
Barbara Varnum-Finney ◽  
Sanjay R. Srivatsan ◽  
Stacey Dozono ◽  
Olivia Waltner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mouse Embryo ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors

3006 – SINGLE CELL MAP OF THE EMERGENCE OF HUMAN HEMATOPOIETIC STEM CELLS FROM HEMOGENIC ENDOTHELIUM

2020 ◽  
Vol 88 ◽  
pp. S39
Author(s):  
Sandra Capellera-Garcia ◽  
Vincenzo Calvanese ◽  
Feiyang Ma ◽  
Iman Fares ◽  
Simone Liebscher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem

Cell staining for sorting of hematopoietic stem cells (HSC) and myeloid progenitors and isolating RNA from sorted cells

2006 ◽  
Author(s):  
Hideyo Hirai ◽  
Pu Zhang ◽  
Tajhal Dayaram ◽  
Christopher Hetherington ◽  
Shin-ichi Mizuno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Cell Staining ◽  
Myeloid Progenitors
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