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Article ; Online: Blood Vessel Resident Human Stem Cells in Health and Disease.

Craig, David J / James, Aaron W / Wang, Yiyun / Tavian, Manuela / Crisan, Mihaela / Péault, Bruno M

2022 Volume 11, Issue 1, Page(s) 35–43

Abstract: The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and tissues. Moreover, some blood vessels are home to essential stem-like cells, a classic ...

Abstract	The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and tissues. Moreover, some blood vessels are home to essential stem-like cells, a classic example being the existence in the embryo of hemogenic endothelial cells at the origin of definitive hematopoiesis. In recent years, microvascular pericytes and adventitial perivascular cells were observed to include multi-lineage progenitor cells involved not only in organ turnover and regeneration but also in pathologic remodeling, including fibrosis and atherosclerosis. These perivascular mesodermal elements were identified as native forerunners of mesenchymal stem cells. We have presented in this brief review our current knowledge on vessel wall-associated tissue remodeling cells with respect to discriminating phenotypes, functional diversity in health and disease, and potential therapeutic interest.
MeSH term(s)	Endothelial Cells ; Humans ; Mesenchymal Stem Cells/physiology ; Pericytes ; Peripheral Blood Stem Cells ; Stem Cells/physiology
Language	English
Publishing date	2022-05-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1093/stcltm/szab001
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Article ; Online: Isolation of Mouse Megakaryocyte Progenitors.

Kimmerlin, Quentin / Tavian, Manuela / Gachet, Christian / Lanza, François / Brouard, Nathalie

Journal of visualized experiments : JoVE

2021 , Issue 171

Abstract: Bone marrow megakaryocytes are large polyploid cells that ensure the production of blood platelets. They arise from hematopoietic stem cells through megakaryopoiesis. The final stages of this process are complex and classically involve the bipotent ... ...

Abstract	Bone marrow megakaryocytes are large polyploid cells that ensure the production of blood platelets. They arise from hematopoietic stem cells through megakaryopoiesis. The final stages of this process are complex and classically involve the bipotent Megakaryocyte-Erythrocyte Progenitors (MEP) and the unipotent Megakaryocyte Progenitors (MKp). These populations precede the formation of bona fide megakaryocytes and, as such, their isolation and characterization could allow for the robust and unbiased analysis of megakaryocyte formation. This protocol presents in detail the procedure to collect hematopoietic cells from mouse bone marrow, the enrichment of hematopoietic progenitors through magnetic depletion and finally a cell sorting strategy that yield highly purified MEP and MKp populations. First, bone marrow cells are collected from the femur, the tibia, and also the iliac crest, a bone that contains a high number of hematopoietic progenitors. The use of iliac crest bones drastically increases the total cell number obtained per mouse and thus contributes to a more ethical use of animals. A magnetic lineage depletion was optimized using 450 nm magnetic beads allowing a very efficient cell sorting by flow cytometry. Finally, the protocol presents the labeling and gating strategy for the sorting of the two highly purified megakaryocyte progenitor populations: MEP (Lin
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Cell Differentiation/physiology ; Cell Separation/methods ; Hematopoietic Stem Cells/cytology ; Megakaryocyte Progenitor Cells/cytology ; Megakaryocytes/cytology ; Mice
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/62498
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Article ; Online: Macrophage depletion overcomes human hematopoietic cell engraftment failure in zebrafish embryo.

El Omar, Reine / Abdellaoui, Naoill / Coulibaly, Safiatou T / Fontenille, Laura / Lanza, François / Gachet, Christian / Freund, Jean-Noel / Negroni, Matteo / Kissa, Karima / Tavian, Manuela

Cell death & disease

2024 Volume 15, Issue 5, Page(s) 305

Abstract: Zebrafish is widely adopted as a grafting model for studying human development and diseases. Current zebrafish xenotransplantations are performed using embryo recipients, as the adaptive immune system, responsible for host versus graft rejection, only ... ...

Abstract	Zebrafish is widely adopted as a grafting model for studying human development and diseases. Current zebrafish xenotransplantations are performed using embryo recipients, as the adaptive immune system, responsible for host versus graft rejection, only reaches maturity at juvenile stage. However, transplanted primary human hematopoietic stem/progenitor cells (HSC) rapidly disappear even in zebrafish embryos, suggesting that another barrier to transplantation exists before the onset of adaptive immunity. Here, using a labelled macrophage zebrafish line, we demonstrated that engraftment of human HSC induces a massive recruitment of macrophages which rapidly phagocyte transplanted cells. Macrophages depletion, by chemical or pharmacological treatments, significantly improved the uptake and survival of transplanted cells, demonstrating the crucial implication of these innate immune cells for the successful engraftment of human cells in zebrafish. Beyond identifying the reasons for human hematopoietic cell engraftment failure, this work images the fate of human cells in real time over several days in macrophage-depleted zebrafish embryos.
MeSH term(s)	Zebrafish/embryology ; Animals ; Macrophages/metabolism ; Humans ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Embryo, Nonmammalian/metabolism ; Transplantation, Heterologous ; Phagocytosis
Language	English
Publishing date	2024-05-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-024-06682-x
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Article ; Online: Multiomics of three hematological malignancies in a patient reveal their origin from clonal hematopoietic stem cells.

Mayeur, Sylvain / Molitor, Anne / Miguet, Laurent / Rigolot, Lucie / Naegely, Lydie / Stemmelen, Tristan / Meyer, Sébastien / Toussaint, Elise / Vallat, Laurent / Eischen, Alice / Chenard, Marie-Pierre / Tavian, Manuela / Bahram, Seiamak / Carapito, Raphael / Nicolae, Alina

Blood cancer journal

2023 Volume 13, Issue 1, Page(s) 118

MeSH term(s)	Humans ; Multiomics ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/pathology ; Hematopoietic Stem Cells/pathology
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-023-00892-w
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Article ; Online: CD32 captures committed haemogenic endothelial cells during human embryonic development.

Nature cell biology

2024

Abstract: During embryonic development, blood cells emerge from specialized endothelial cells, named haemogenic endothelial cells (HECs). As HECs are rare and only transiently found in early developing embryos, it remains difficult to distinguish them from ... ...

Abstract	During embryonic development, blood cells emerge from specialized endothelial cells, named haemogenic endothelial cells (HECs). As HECs are rare and only transiently found in early developing embryos, it remains difficult to distinguish them from endothelial cells. Here we performed transcriptomic analysis of 28- to 32-day human embryos and observed that the expression of Fc receptor CD32 (FCGR2B) is highly enriched in the endothelial cell population that contains HECs. Functional analyses using human embryonic and human pluripotent stem cell-derived endothelial cells revealed that robust multilineage haematopoietic potential is harboured within CD32
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-024-01403-0
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Isolation of mouse megakaryocyte progenitors

Kimmerlin, Quentin / Tavian, Manuela / Gachet, Christian / Lanza, François / Brouard, Nathalie

Journal of visualized experiments. 2021 May 20, , no. 171

2021

Abstract	Bone marrow megakaryocytes are large polyploid cells that ensure the production of blood platelets. They arise from hematopoietic stem cells through megakaryopoiesis. The final stages of this process are complex and classically involve the bipotent Megakaryocyte-Erythrocyte Progenitors (MEP) and the unipotent Megakaryocyte Progenitors (MKp). These populations precede the formation of bona fide megakaryocytes and, as such, their isolation and characterization could allow for the robust and unbiased analysis of megakaryocyte formation. This protocol presents in detail the procedure to collect hematopoietic cells from mouse bone marrow, the enrichment of hematopoietic progenitors through magnetic depletion and finally a cell sorting strategy that yield highly purified MEP and MKp populations. First, bone marrow cells are collected from the femur, the tibia, and also the iliac crest, a bone that contains a high number of hematopoietic progenitors. The use of iliac crest bones drastically increases the total cell number obtained per mouse and thus contributes to a more ethical use of animals. A magnetic lineage depletion was optimized using 450 nm magnetic beads allowing a very efficient cell sorting by flow cytometry. Finally, the protocol presents the labeling and gating strategy for the sorting of the two highly purified megakaryocyte progenitor populations: MEP (Lin-Sca-1-c-Kit+CD16/32-CD150+CD9dim) and MKp (Lin- Sca-1-c-Kit+CD16/32-CD150+CD9bright). This technique is easy to implement and provides enough cellular material to perform i) molecular characterization for a deeper knowledge of their identity and biology, ii) in vitro differentiation assays, that will provide a better understanding of the mechanisms of maturation of megakaryocytes, or iii) in vitro models of interaction with their microenvironment.
Keywords	bone marrow ; ethics ; femur ; flow cytometry ; ilium ; magnetism ; megakaryocytes ; mice ; polyploidy ; tibia
Language	English
Dates of publication	2021-0520
Size	p. e62498.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/62498
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Article ; Online: Renin-angiotensin system is involved in embryonic emergence of hematopoietic stem/progenitor cells.

Julien, Emmanuelle / Biasch, Katia / El Omar, Reine / Freund, Jean-Noël / Gachet, Christian / Lanza, François / Tavian, Manuela

Stem cells (Dayton, Ohio)

2021 Volume 39, Issue 5, Page(s) 636–649

Abstract: Angiotensin-converting enzyme (ACE), a key element of the renin-angiotensin system (RAS), has recently been identified as a new marker of both adult and embryonic human hematopoietic stem/progenitor cells (HSPCs). However, whether a full renin- ... ...

Abstract	Angiotensin-converting enzyme (ACE), a key element of the renin-angiotensin system (RAS), has recently been identified as a new marker of both adult and embryonic human hematopoietic stem/progenitor cells (HSPCs). However, whether a full renin-angiotensin pathway is locally present during the hematopoietic emergence is still an open question. In the present study, we show that this enzyme is expressed by hematopoietic progenitors in the developing mouse embryo. Furthermore, ACE and the other elements of RAS-namely angiotensinogen, renin, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors-are expressed in the paraaortic splanchnopleura (P-Sp) and in its derivative, the aorta-gonad-mesonephros region, both in human and mouse embryos. Their localization is compatible with the existence of a local autocrine and/or paracrine RAS in these hemogenic sites. in vitro perturbation of the RAS by administration of a specific AT1 receptor antagonist inhibits almost totally the generation of blood CD45-positive cells from dissected P-Sp, implying that angiotensin II signaling is necessary for the emergence of hematopoietic cells. Conversely, addition of exogenous angiotensin II peptide stimulates hematopoiesis in culture, with an increase in the number of immature c-Kit
MeSH term(s)	Angiotensin II/genetics ; Angiotensinogen/genetics ; Animals ; Aorta/growth & development ; Gene Expression Regulation, Developmental/genetics ; Hematopoiesis/drug effects ; Hematopoiesis/genetics ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Humans ; Leukocyte Common Antigens/genetics ; Mice ; Peptides/pharmacology ; Peptidyl-Dipeptidase A/genetics ; Receptor, Angiotensin, Type 1/genetics ; Receptor, Angiotensin, Type 2/genetics ; Renin/genetics ; Renin-Angiotensin System/genetics ; Signal Transduction/drug effects ; Stem Cells/cytology
Chemical Substances	Peptides ; Receptor, Angiotensin, Type 1 ; Receptor, Angiotensin, Type 2 ; Angiotensinogen (11002-13-4) ; Angiotensin II (11128-99-7) ; Leukocyte Common Antigens (EC 3.1.3.48) ; PTPRC protein, human (EC 3.1.3.48) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.3339
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Zs.A 1894: Show issues

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Article ; Online: Origin of the hematopoietic system in the human embryo.

Julien, Emmanuelle / El Omar, Reine / Tavian, Manuela

FEBS letters

2016 Volume 590, Issue 22, Page(s) 3987–4001

Abstract: The continuous generation of blood cells throughout life relies on the existence of hematopoietic stem cells (HSC) generated during embryogenesis. Given the importance of HSC transplantation in cell-based therapeutic approaches, considerable efforts have ...

Abstract	The continuous generation of blood cells throughout life relies on the existence of hematopoietic stem cells (HSC) generated during embryogenesis. Given the importance of HSC transplantation in cell-based therapeutic approaches, considerable efforts have been made toward understanding the developmental origins of embryonic HSC. Adult-type HSC are first generated in the aorta-gonad-mesonephros (AGM) region between days 27 and 40 of human embryonic development, but an elusive blood-forming potential is present earlier in the underlying splanchnopleura. It is relatively well accepted that the HSC emerge in the AGM through a hemogenic endothelium, but the direct precursor of this cell type remains to be clearly identified. This review is intended to summarize the recent advances made to understand the origins of hematopoietic stem cells in the early human embryo. In addition, we discuss in detail the discovery of the angiotensin-converting enzyme (ACE) as a novel marker of human HSC and of prehematopoietic precursors inside the embryo.
MeSH term(s)	Adult ; Animals ; Aorta/growth & development ; Embryo, Mammalian ; Embryonic Development/genetics ; Female ; Gonads/growth & development ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/cytology ; Humans ; Mice ; Peptidyl-Dipeptidase A/genetics ; Pregnancy
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.12389
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Zs.B 282: Show issues

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Article ; Online: CDX2 regulates ACE expression in blood development and leukemia cells.

El Omar, Reine / Julien, Emmanuelle / Biasch, Katia / Guffroy, Blandine / Lioure, Bruno / Vallat, Laurent / Gross, Isabelle / Domon-Dell, Claire / Lanza, François / Gachet, Christian / Negroni, Matteo / Freund, Jean-Noël / Tavian, Manuela

Blood advances

2021 Volume 5, Issue 7, Page(s) 2012–2016

MeSH term(s)	CDX2 Transcription Factor ; Homeodomain Proteins/genetics ; Humans ; Leukemia, Myeloid, Acute
Chemical Substances	CDX2 Transcription Factor ; CDX2 protein, human ; Homeodomain Proteins
Language	English
Publishing date	2021-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003563
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Zs.A 7153: Show issues

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Article ; Online: CDX2 expression in the hematopoietic lineage promotes leukemogenesis via TGFβ inhibition.

Galland, Ava / Gourain, Victor / Habbas, Karima / Güler, Yonca / Martin, Elisabeth / Ebel, Claudine / Tavian, Manuela / Vallat, Laurent / Chenard, Marie-Pierre / Mauvieux, Laurent / Freund, Jean-Noël / Duluc, Isabelle / Domon-Dell, Claire

Molecular oncology

2021 Volume 15, Issue 9, Page(s) 2318–2329

Abstract: The intestine-specific caudal-related homeobox gene-2 (CDX2) homeobox gene, while being a tumor suppressor in the gut, is ectopically expressed in a large proportion of acute leukemia and is associated with poor prognosis. Here, we report that turning on ...

Abstract	The intestine-specific caudal-related homeobox gene-2 (CDX2) homeobox gene, while being a tumor suppressor in the gut, is ectopically expressed in a large proportion of acute leukemia and is associated with poor prognosis. Here, we report that turning on human CDX2 expression in the hematopoietic lineage of mice induces acute monoblastic leukemia, characterized by the decrease in erythroid and lymphoid cells at the benefit of immature monocytic and granulocytic cells. One of the highly stimulated genes in leukemic bone marrow cells was BMP and activin membrane-bound inhibitor (Bambi), an inhibitor of transforming growth factor-β (TGF-β) signaling. The CDX2 protein was shown to bind to and activate the transcription of the human BAMBI promoter. Moreover, in a leukemic cell line established from CDX2-expressing mice, reducing the levels of CDX2 or Bambi stimulated the TGF-β-dependent expression of Cd11b, a marker of monocyte maturation. Taken together, this work demonstrates the strong oncogenic potential of the homeobox gene CDX2 in the hematopoietic lineage, in contrast with its physiological tumor suppressor activity exerted in the gut. It also reveals, through BAMBI and TGF-β signaling, the involvement of CDX2 in the perturbation of the interactions between leukemia cells and their microenvironment.
MeSH term(s)	Animals ; CD11b Antigen/genetics ; CDX2 Transcription Factor/genetics ; Cell Lineage ; Humans ; Leukemia, Monocytic, Acute/genetics ; Leukemia, Monocytic, Acute/pathology ; Membrane Proteins/genetics ; Mice ; Signal Transduction ; Transforming Growth Factor beta/antagonists & inhibitors ; Tumor Microenvironment
Chemical Substances	BAMBI protein, human ; CD11b Antigen ; CDX2 Transcription Factor ; CDX2 protein, human ; ITGAM protein, human ; Membrane Proteins ; Transforming Growth Factor beta
Language	English
Publishing date	2021-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.12982
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