Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation.
The blast colony-forming cell (BL-CFC) was identified as an equivalent to the hemangioblast during in vitro embryonic stem (ES) cell differentiation. However, the molecular mechanisms underlying the generation of the BL-CFC remain largely unknown. Here we report the isolation of mouse lysocardiolipin acyltransferase (Lycat) based on homology to zebrafish lycat, a candidate gene for the cloche locus. Mouse Lycat is expressed in hematopoietic organs and is enriched in the Lin(-)C-Kit(+)Sca-1(+) hematopoietic stem cells in bone marrow and in the Flk1(+)/hCD4(+)(Scl(+)) hemangioblast population in embryoid bodies. The forced Lycat transgene leads to increased messenger RNA expression of hematopoietic and endothelial genes as well as increased blast colonies and their progenies, endothelial and hematopoietic lineages. The Lycat small interfering RNA transgene leads to a decrease expression of hematopoietic and endothelial genes. An unbiased genomewide microarray analysis further substantiates that the forced Lycat transgene specifically up-regulates a set of genes related to hemangioblasts and hematopoietic and endothelial lineages. Therefore, mouse Lycat plays an important role in the early specification of hematopoietic and endothelial cells, probably acting at the level of the hemangioblast.
Wang
Chengyan
C
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
Faloon
Patrick W
PW
Tan
Zhijia
Z
Lv
Yaxin
Y
Zhang
Pengbo
P
Ge
Yu
Y
Deng
Hongkui
H
Xiong
Jing-Wei
JW
D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D030781:Organisms, Genetically Modified; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D015027:Zebrafish / Q000235:genetics
D002308:Cardiolipins; D034741:RNA, Small Interfering; D000217:Acyltransferases; C525544:lysocardiolipin acyltransferase, mouse