Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation

Wang, Chengyan; Faloon, Patrick W.; Tan, Zhijia; Lv, Yaxin; Ge, Yufeng; Deng, Hongkui; Xiong, Jing-Wei

doi:10.1182/blood-2007-04-086827

Cited by 37 publications

(35 citation statements)

References 88 publications

(115 reference statements)

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“…This enzyme was identified as acyllysocardiolipin acyltransferase-1 (ALCAT1) (23). Recently it was shown that ALCAT1 expression in endothelial and hematopoietic lineages resulted in elevated hematopoietic and endothelial genes and increased blast colonies and their progenies (24,25). The opposite effect was observed with ALCAT1 small interfering RNA indicating that ALCAT1 may play a role in the early specification of hematopoietic and endothelial cells (24,25).…”

Section: Cardiolipin (Cl)mentioning

confidence: 88%

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

Taylor

Hatch

2009

Journal of Biological Chemistry

100

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Here we report the identification of a previously uncharacterized human protein as the human monolysocardiolipin acyltransferase-1 (MLCL AT-1). Pig liver mitochondria were treated with n-butyl alcohol followed by Q-Sepharose chromatography, preparative gel electrophoresis, cytidine diphosphate-1,2-diacyl-sn-glycerol-Sepharose chromatography, and finally monolysocardiolipin-adriamycin-agarose affinity chromatography. Elution with either monolysocardiolipin or linoleoyl coenzyme A revealed a major band at 74 kDa with high specific activity (2,300 pmol/min/mg) for the acylation of monolysocardiolipin to cardiolipin using Cardiolipin (CL)2 is a major phospholipid found in mammalian mitochondria with a multitude of biological functions (reviewed in Refs. 1-7). For example, CL is responsible for modulation of the activity of several mitochondrial enzymes involved in the generation of ATP (reviewed in Refs. 8, 9). In fact, it has been suggested that CL is the "glue" that holds the mitochondrial respiratory complex together (10). The role of CL in genetic diseases such as Barth syndrome, a rare X-linked genetic disorder, is beginning to emerge. Barth syndrome is the only known genetic disease in which the specific biochemical defect is a reduction in CL and accumulation of monolysocardiolipin (MLCL) caused by mutations in the TAZ gene (reviewed in Refs. 2,7,11,12). In addition, the role that CL plays in apoptosis is now well documented (reviewed in Ref. 13). Thus, maintenance of the appropriate content and fatty acyl composition of CL in mitochondria is essential for proper cellular function.The molecular composition of CL appears to be important for the biological function of CL. In general, there is a selection of a particular kind of fatty acid as well as restriction of the number of fatty acid species (14). The major tetra-acyl molecular species found in rat liver (ϳ57% of total) and bovine heart (ϳ48% of total) are 18:2 in each of the four fatty acyl positions of the cardiolipin molecule. Remodeling of CL is essential to obtain this enrichment of CL with linoleate because CL synthase has no molecular species substrate specificity for cytidine-5Ј-diphosphate-1,2-diacyl-sn-glycerol (15). In addition, the species pattern of CL precursors is similar enough to imply that the enzymes of the CL synthetic pathway are not molecular species-selective (16). Alterations in the molecular composition of CL are associated with various disease states, including diabetes and Barth syndrome (17,18

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Section: Cardiolipin (Cl)mentioning

confidence: 88%

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

Taylor

Hatch

2009

Journal of Biological Chemistry

100

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“…We have recently identified lysocardiolipin acyltransferase (lycat) gene from the cloche m39 deletion interval, but we have not found any causative mutations in the coding region of lycat from two ENUinduced cloche alleles (cloche fv087b and cloche m378 ). Therefore, it remains to be determined how lycat is related to the cloche gene (Xiong et al, 2008;Wang et al, 2007). We have examined lycat function using antisense morpholino knockdown and misexpression of lycat in zebrafish embryos and found that lycat is absolutely required for both endothelial and hematopoietic lineage development and lycat acts upstream to several known hemangioblastic marker genes (Xiong et al, 2008).…”

Section: Molecular Pathways Involved In Hemangioblast Developmentmentioning

confidence: 99%

“…We have examined lycat function using antisense morpholino knockdown and misexpression of lycat in zebrafish embryos and found that lycat is absolutely required for both endothelial and hematopoietic lineage development and lycat acts upstream to several known hemangioblastic marker genes (Xiong et al, 2008). Furthermore, mouse Lycat gene also plays essential roles in hemangioblast, hematopoietic, and endothelial lineage development using loss-of-function and gain-of-function analyses in mouse ESCs differentiation system (Wang et al, 2007). In addition, misexpression of mouse Lycat in ESCs leads to up-regulation of a panel of hemangioblastic marker genes in EBs (Wang et al, 2007).…”

Section: Molecular Pathways Involved In Hemangioblast Developmentmentioning

confidence: 99%

“…Furthermore, mouse Lycat gene also plays essential roles in hemangioblast, hematopoietic, and endothelial lineage development using loss-of-function and gain-of-function analyses in mouse ESCs differentiation system (Wang et al, 2007). In addition, misexpression of mouse Lycat in ESCs leads to up-regulation of a panel of hemangioblastic marker genes in EBs (Wang et al, 2007). Therefore, lycat is a novel essential gene for hemangioblast development in zebrafish embryos and mouse ESCs.…”

Section: Molecular Pathways Involved In Hemangioblast Developmentmentioning

confidence: 99%

“…Inactivation of a single VEGF allele, of VEGFR-2 (flk1) or of phospholipase C-gamma 1 (Plcg1) in mice has reduced angioblasts and hematopoietic stem cells (HSCs; Shalaby et al, 1995Shalaby et al, , 1997Carmeliet et al, 1996;Ferrara et al, 1996;Damert et al, 2002;Liao et al, 2002). Genetically engineered ESCs are assessed for their ability to differentiate into BL-CFCs in vitro, by which Flk1, Scl, Runx1, Hhex, Mixl1, Bmp4, Smad1, Gata2, and lysocardiolipin acyltransferase (Lycat) are shown to be essential for the generation of BL-CFCs (Hidaka et al, 1999;Schuh et al, 1999;Faloon et al, 2000;Robertson et al, 2000;Chung et al, 2002;Lacaud et al, 2002Lacaud et al, , 2004Lugus et al, 2007;Wang et al, 2007;Zafonte et al, 2007). Zebrafish cloche mutant affects both endothelial and hematopoietic lineages (Stainier et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Molecular and developmental biology of the hemangioblast

Xiong

2008

Developmental Dynamics

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The hemangioblast hypothesis was proposed a century ago. The existence of hemangioblasts is now demonstrated in mouse and human embryonic stem cell (ESC) -derived embryoid bodies (EBs), in the mouse and zebrafish gastrula, and in adults. The hemangioblast is believed to derive from mesodermal cells, and is enriched in the Bry ؉ Flk1 ؉ and Flk1 ؉ Scl ؉ cell populations in EBs and in the posterior primitive streak of the mouse gastrula and in the ventral mesoderm of the zebrafish gastrula. However, recent studies suggest that the hemangioblast does not give rise to all endothelial and hematopoietic lineages in mouse and zebrafish embryos. Although several signaling pathways are known to involve the generation of hemangioblasts, it remains largely unknown how the hemangioblast is formed and what are the master genes controlling hemangioblast development. This review will summarize our current knowledge, challenges, and future directions on molecular and developmental aspects of the hemangioblast.

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The Hemangioblast: From Concept to Authentication

Cao

Yao

2011

The Anatomical Record

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The hemangioblast hypothesis has been hotly debated for over a century. Hemangioblasts are defined as multipotent cells that can give rise to both hematopoietic cells and endothelial cells. The existence of hemangioblasts has now been confirmed and many important molecules and several signaling pathways are involved in their generation and differentiation. Fibroblast growth factor, renin-angiotensin system and runt-related transcription factor 1 (Runx1) direct the formation of hemangioblasts through highly selective gene expression patterns. On the other hand, the hemogenic endothelium theory and a newly discovered pattern of hematopoietic/endothelial differentiation make the genesis of hemangioblasts more complicated. But how hemangioblasts are formed and how hematopoietic cells or endothelial cells are derived from remains largely unknown. Here we summarize the current knowledge of the signaling pathways and molecules involved in hemangioblast development and suggest some future clinical applications. Anat Rec, 294:580-588, 2011. V V C 2011 Wiley-Liss, Inc.

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Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation

Cited by 37 publications

References 88 publications

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

Molecular and developmental biology of the hemangioblast

The Hemangioblast: From Concept to Authentication

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