A Transcriptional Switch Point During Hematopoietic Stem and Progenitor Cell Ontogeny

造血干细胞和祖细胞个体发育过程中的转录转换点

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作者:Daisuke Sugiyama, Anagha Joshi, Kasem Kulkeaw, Keai Sinn Tan, Tomoko Yokoo-Inoue, Chiyo Mizuochi-Yanagi, Kaori Yasuda, Atsushi Doi, Tadafumi Iino, Masayoshi Itoh, Sayaka Nagao-Sato, Kenzaburo Tani, Koichi Akashi, Yoshihide Hayashizaki, Harukazu Suzuki, Hideya Kawaji, Piero Carninci, Alistair R R For

Abstract

During mammalian embryogenesis, hematopoietic stem and progenitor cells (HSPCs) originate from mesoderm-derived endothelial cells in the aorta-gonad-mesonephros (AGM) region and placenta (PL). Later, HSPCs expand in fetal liver (FL) and migrate to bone marrow (BM) shortly before birth. Understanding global transcriptional regulation governing HSPC emergence from embryonic stem/induced pluripotent stem cells is necessary to devise clinical applications, such as novel transplantation approaches. In this study, to assess transcriptional dynamics during development, we performed cap analysis of gene expression on 10 developmental murine HSPC populations isolated from the AGM region, PL, FL, and BM and identified 15,681 transcripts across HSPC ontogeny. We performed microarray analysis of AGM-derived HSPCs at 9.5 and 10.5 days postcoitum (dpc) and identified 40 differentially expressed genes, 23 confirmed as significantly changed by real-time polymerase chain reaction. We conclude that a transcriptional switch point occurs in HSPC ontogeny between 9.5 and 10.5 dpc in the AGM region.

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