Talk:Cardiovascular System - Blood Development
| About Discussion Pages |
|---|
Glossary Links
Cite this page: Hill, M.A. (2024, April 16) Embryology Cardiovascular System - Blood Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Cardiovascular_System_-_Blood_Development |
2010
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans
Science. 2010 Dec 17;330(6011):1695-9.
Mold JE, Venkatasubrahmanyam S, Burt TD, Michaëlsson J, Rivera JM, Galkina SA, Weinberg K, Stoddart CA, McCune JM.
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143-1234, USA. Erratum in:
Science. 2011 Feb 4;331(6017):534. Comment in:
Science. 2010 Dec 17;330(6011):1635-6.
Abstract
Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.
PMID: 21164017 http://www.ncbi.nlm.nih.gov/pubmed/21164017
Erythropoietin couples hematopoiesis with bone formation
PLoS One. 2010 May 27;5(5):e10853.
Shiozawa Y, Jung Y, Ziegler AM, Pedersen EA, Wang J, Wang Z, Song J, Wang J, Lee CH, Sud S, Pienta KJ, Krebsbach PH, Taichman RS.
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
Abstract BACKGROUND: It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from marrow stromal cells. This suggests that HSCs participate in bone formation where the molecular basis for this activity is the production of BMP2 and BMP6 by HSCs. Yet, what stimulates HSCs to produce BMPs is unclear.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that erythropoietin (Epo) activates Jak-Stat signaling pathways in HSCs which leads to the production of BMPs. Critically, Epo also directly activates mesenchymal cells to form osteoblasts in vitro, which in vivo leads to bone formation. Importantly, Epo first activates osteoclastogenesis which is later followed by osteoblastogenesis that is induced by either Epo directly or the expression of BMPs by HSCs to form bone.
CONCLUSIONS/SIGNIFICANCE: These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow.
Figure 7. Coupling of hematopoiesis with osteopoiesis by Epo.
PMID: 20523730 http://www.ncbi.nlm.nih.gov/pubmed/20523730
Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells
Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7799-804. Epub 2010 Apr 12.
Chou S, Lodish HF.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Abstract Previously we showed that the ~2% of fetal liver cells reactive with an anti-CD3epsilon monoclonal antibody support ex vivo expansion of both fetal liver and bone marrow hematopoietic stem cells (HSCs); these cells express two proteins important for HSC ex vivo expansion, IGF2, and angiopoietin-like 3. Here we show that these cells do not express any CD3 protein and are not T cells; rather, we purified these HSC-supportive stromal cells based on the surface phenotype of SCF(+)DLK(+). Competitive repopulating experiments show that SCF(+)DLK(+) cells support the maintenance of HSCs in ex vivo culture. These are the principal fetal liver cells that express not only angiopoietin-like 3 and IGF2, but also SCF and thrombopoietin, two other growth factors important for HSC expansion. They are also the principal fetal liver cells that express CXCL12, a factor required for HSC homing, and also alpha-fetoprotein (AFP), indicating that they are fetal hepatic stem or progenitor cells. Immunocytochemistry shows that >93% of the SCF(+) cells express DLK and Angptl3, and a portion of SCF(+) cells also expresses CXCL12. Thus SCF(+)DLK(+) cells are a highly homogenous population that express a complete set of factors for HSC expansion and are likely the primary stromal cells that support HSC expansion in the fetal liver.
PMID: 20385801 http://www.ncbi.nlm.nih.gov/pubmed/20385801
2009
Endochondral ossification is required for haematopoietic stem-cell niche formation
Nature. 2009 Jan 22;457(7228):490-4. Epub 2008 Dec 10.
Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT, Wei K, Helms JA, Kuo CJ, Kraft DL, Weissman IL.
Department of Pathology, Developmental Biology and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, California, USA. chazchan@stanford.edu
Abstract Little is known about the formation of niches, local micro-environments required for stem-cell maintenance. Here we develop an in vivo assay for adult haematopoietic stem-cell (HSC) niche formation. With this assay, we identified a population of progenitor cells with surface markers CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1.1(-) (CD105(+)Thy1(-)) that, when sorted from 15.5 days post-coitum fetal bones and transplanted under the adult mouse kidney capsule, could recruit host-derived blood vessels, produce donor-derived ectopic bones through a cartilage intermediate and generate a marrow cavity populated by host-derived long-term reconstituting HSC (LT-HSC). In contrast, CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1(+) (CD105(+)Thy1(+)) fetal bone progenitors form bone that does not contain a marrow cavity. Suppressing expression of factors involved in endochondral ossification, such as osterix and vascular endothelial growth factor (VEGF), inhibited niche generation. CD105(+)Thy1(-) progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification formed only bone without marrow in our assay. Collectively, our data implicate endochondral ossification, bone formation that proceeds through a cartilage intermediate, as a requirement for adult HSC niche formation.
PMID: 19078959 http://www.ncbi.nlm.nih.gov/pubmed/19078959
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648141
Sonic hedgehog expands diaphyseal trabecular bone altering bone marrow niche and lymphocyte compartment
Mol Ther. 2009 Aug;17(8):1442-52. Epub 2009 May 12.
Kiuru M, Hidaka C, Hubner RH, Solomon J, Krause A, Leopold PL, Crystal RG.
Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York 10065, USA.
Abstract
Bone marrow contains distinct microenvironments that regulate hematopoietic stem cells (HSCs). The endosteal HSC niche includes osteoblasts, mineral, and extracellular matrix proteins that interact through various molecular signals to control HSCs. Sonic hedgehog (Shh) is a morphogen involved in the regulation of skeletal development and hematopoiesis, but the effects of Shh on bone in relation to the HSC niche are not well understood. We demonstrate that systemic overexpression of Shh in mice increases osteoblast number with the resultant formation of new trabeculae in the femoral diaphysis. Suggestive of a functional change in the hematopoietic niche, numbers of Lin(-) Sca-1(+) c-Kit(+) cells with hematopoietic progenitor function expand, although cells with in vivo repopulating capacity in the wild-type environment do not increase. Instead, Shh mediates a decrease in number of bone marrow lymphocytes accompanied by a decreased expression of stromal-derived growth factor 1 (SDF-1) and a decrease in Flk2-expressing Lin(-) Sca-1(+) c-Kit(+) cells, indicating a modulation of early lymphopoiesis. This is caused by a microenvironment-induced mechanism as Shh treatment of bone marrow recipients, but not donors, results in a dramatic depletion of lymphocytes. Together, these data suggest that Shh mediates alterations in the bone marrow hematopoietic niche affecting the early lymphoid differentiation.
PMID: 19436267
2008
Fate tracing reveals the endothelial origin of hematopoietic stem cells
Cell Stem Cell. 2008 Dec 4;3(6):625-36.
Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, Becker MS, Zanetta L, Dejana E, Gasson JC, Tallquist MD, Iruela-Arispe ML.
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Abstract Hematopoietic stem cells (HSCs) originate within the aortic-gonado-mesonephros (AGM) region of the midgestation embryo, but the cell type responsible for their emergence is unknown since critical hematopoietic factors are expressed in both the AGM endothelium and its underlying mesenchyme. Here we employ a temporally restricted genetic tracing strategy to selectively label the endothelium, and separately its underlying mesenchyme, during AGM development. Lineage tracing endothelium, via an inducible VE-cadherin Cre line, reveals that the endothelium is capable of HSC emergence. The endothelial progeny migrate to the fetal liver, and later to the bone marrow, and are capable of expansion, self-renewal, and multilineage hematopoietic differentiation. HSC capacity is exclusively endothelial, as ex vivo analyses demonstrate lack of VE-cadherin Cre induction in circulating and fetal liver hematopoietic populations. Moreover, AGM mesenchyme, as selectively traced via a myocardin Cre line, is incapable of hematopoiesis. Our genetic tracing strategy therefore reveals an endothelial origin of HSCs.
PMID: 19041779 http://www.ncbi.nlm.nih.gov/pubmed/19041779
2004
Cytoskeletal influences on nuclear shape in granulocytic HL-60 cells
BMC Cell Biol. 2004 Aug 19;5:30.
Olins AL, Olins DE.
Department of Biology, Bowdoin College, Brunswick, Maine 04011, USA. aolins@bowdoin.edu
Abstract
BACKGROUND: During granulopoiesis in the bone marrow, the nucleus differentiates from ovoid to lobulated shape. Addition of retinoic acid (RA) to leukemic HL-60 cells induces development of lobulated nuclei, furnishing a convenient model system for nuclear differentiation during granulopoiesis. Previous studies from our laboratory have implicated nuclear envelope composition as playing important roles in nuclear shape changes. Specifically noted were: 1) a paucity of lamins A/C and B1 in the undifferentiated and RA treated cell forms; 2) an elevation of lamin B receptor (LBR) during induced granulopoiesis.
RESULTS: The present study demonstrates that perturbation of cytoskeletal elements influences nuclear differentiation of HL-60 cells. Because of cytotoxicity from prolonged exposure to cytoskeleton-modifying drugs, most studies were performed with a Bcl-2 overexpressing HL-60 subline. We have found that: 1) nocodazole prevents RA induction of lobulation; 2) taxol induces lobulation and micronuclear formation, even in the absence of RA; 3) cytochalasin D does not inhibit RA induced nuclear lobulation, and prolonged exposure induces nuclear shape changes in the absence of RA.
CONCLUSIONS: The present results, in the context of earlier data and models, suggest a mechanism for granulocytic nuclear lobulation. Our current hypothesis is that the nuclear shape change involves factors that increase the flexibility of the nuclear envelope (reduced lamin content), augment connections to the underlying heterochromatin (increased levels of LBR) and promote distortions imposed by the cytoskeleton (microtubule motors creating tension in the nuclear envelope).
PMID: 15317658 http://www.ncbi.nlm.nih.gov/pubmed/15317658
