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Spotlight

In two papers published in Cell, investigators from the Harvard Stem Cell Institute, Massachusetts General Hospital, and Childrens Hospital Boston describe how cloned progenitor cells can differentiate into cardiac muscle, smooth muscle, or endothelial cells.

Research reveals master heart cell

Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, however the lineage of these cell types remains incompletely understood.

"The mechanism of cardiogenesis has fascinated biologists for two centuries," says Stuart Orkin, who led the team of researchers at Childrens Hospital Boston. "Despite beliefs that the different cells had distinct origins, recent animal experiments have suggested that a large proportion of cells in the mature heart share a common ancestry. To investigate this, we isolated cardiac progenitor cells from early stage mouse embryos and followed their differentiation. Expectedly, the majority of these cells differentiated spontaneously into muscle cells that expand and contract the heart's chambers. But, surprisingly, a subset of the cells adapted a smooth muscle cell fate." These results support the existence of a common precursor for cardiovascular lineages in the mammalian heart.

In a separate study, Kenneth Chien, director of the Harvard Stem Cell Institute's cardiovascular disease program and Massachusetts General Hospital's center for cardiovascular research, and his team used genetic fate-mapping studies to document that ES cell-derived multipotent isl1+ cardiovascular precursors can generate each of these diverse cardiovascular cell types in vivo.

"These progenitor cells offer new prospects for drug discovery and suggest a novel strategy for regeneration of cardiovascular tissue," says Chien. "The results suggest an alternative strategy for achieving the regeneration of distinct heart components that are affected in diverse forms of degenerative heart disease."

The next step will be to translate these findings in mouse models into human cells.

Fig. 1. Model of cellular hierarchy of cardiovascular progenitors and their lineage specification.

Moretti A, Chien KR, et al. Cell. Multipotent Embryonic Isl1(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification.

Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR. Multipotent Embryonic Isl1(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification. Cell. 2006 Nov 20; Read Abstract.

Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. Developmental Origin of a Bipotential Myocardial and Smooth Muscle Cell Precursor in the Mammalian Heart. Cell. 2006 Nov 20 Read Abstract.

Review and Commentary Articles

Sosnovik DE, Weissleder R. Emerging concepts in molecular MRI. Curr Opin Biotechnol. 2006 Nov 23 Read Abstract.

Scientific Papers

Blood Disease

Zada AA, Pulikkan JA, Bararia D, Geletu M, Trivedi AK, Balkhi MY, Hiddemann WD, Tenen DG, Behre HM, Behre G. Proteomic discovery of Max as a novel interacting partner of C/EBPalpha: a Myc/Max/Mad link. Leukemia. 2006 Dec;20(12):2137-46. Read Abstract.
Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H, Takatsu K, Tenen DG, Akashi K. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev. 2006 Nov 1;20(21):3010-21. Read Abstract.
Zada AA, Geletu MH, Pulikkan JA, Muller-Tidow C, Reddy VA, Christopeit M, Hiddemann WD, Behre HM, Tenen DG, Behre G. Proteomic analysis of acute promyelocytic leukemia: PML-RARalpha leads to decreased phosphorylation of OP18 at serine 63. Proteomics. 2006 Nov;6(21):5705-19. Read Abstract.

Cancer

Pieretti-Vanmarcke R, Donahoe PK, Pearsall LA, Dinulescu DM, Connolly DC, Halpern EF, Seiden MV, Maclaughlin DT. Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer. Proc Natl Acad Sci USA. 2006 Nov 14;103(46):17426-17431. Read Abstract.

Cardiovascular Disease

Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. Developmental Origin of a Bipotential Myocardial and Smooth Muscle Cell Precursor in the Mammalian Heart. Cell. 2006 Nov 20 Read Abstract.
Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR. Multipotent Embryonic Isl1(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification. Cell. 2006 Nov 20; Read Abstract.
Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2006 Nov 15; Read Abstract.
Yajima T, Yasukawa H, Jeon ES, Xiong D, Dorner A, Iwatate M, Nara M, Zhou H, Summers-Torres D, Hoshijima M, Chien KR, Yoshimura A, Knowlton KU. Innate defense mechanism against virus infection within the cardiac myocyte requiring gp130-STAT3 signaling. Circulation. 2006 Nov 28;114(22):2364-73. Read Abstract.
Hoshijima M, Knoll R, Pashmforoush M, Chien KR. Reversal of calcium cycling defects in advanced heart failure toward molecular therapy. J Am Coll Cardiol. 2006 Nov 7;48(9 Suppl):A15-23. Read Abstract.

Development

Mishima Y, Giraldez AJ, Takeda Y, Fujiwara T, Sakamoto H, Schier AF, Inoue K. Differential Regulation of Germline mRNAs in Soma and Germ Cells by Zebrafish miR-430. Curr Biol. 2006 Nov 7;16(21):2135-42. Read Abstract.
Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. A protein interaction network for pluripotency of embryonic stem cells. Nature. 2006 Nov 16;444(7117):364-8. Read Abstract.

Immunology

Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV. Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol. 2006 Nov 1;177(9):5902-11. Read Abstract.
Campanella GS, Grimm J, Manice LA, Colvin RA, Medoff BD, Wojtkiewicz GR, Weissleder R, Luster AD. Oligomerization of CXCL10 Is Necessary for Endothelial Cell Presentation and In Vivo Activity. J Immunol. 2006 Nov 15;177(10):6991-8. Read Abstract.

Nervous System Diseases

Liu L, Zhao R, Bai Y, Stanish LF, Evans JE, Sanderson MJ, Bonventre JV, Rittenhouse AR. M1 muscarinic receptors inhibit L-type Ca2+ current and M-current by divergent signal transduction cascades. J Neurosci. 2006 Nov 8;26(45):11588-98. Read Abstract.

Skeletal

Lam NP, Li Y, Waldman AB, Brussiau J, Lee PL, Olsen BR, Xu L. Age-dependent increase of discoidin domain receptor 2 and matrix metalloproteinase 13 expression in temporomandibular joint cartilage of type IX and type XI collagen-deficient mice. Arch Oral Biol. 2006 Nov 22 Read Abstract.

The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions.

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