Talk:Cardiovascular System - Blood Development

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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.

http://www.plosone.org/article/slideshow.action?uri=info:doi/10.1371/journal.pone.0010853&imageURI=info:doi/10.1371/journal.pone.0010853.g007

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