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Global re‐organization of replication domains during embryonic stem cell differentiation
Author(s) -
Gilbert David Michael,
Hiratani Ichiro,
Hiratani Mari,
Ryba Tyrone,
Takebayashi ShinIchiro
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.481.1
Subject(s) - embryonic stem cell , biology , microbiology and biotechnology , induced pluripotent stem cell , replication timing , cellular differentiation , replication (statistics) , genetics , dna replication , dna , gene , virology
We constructed high‐resolution replication timing profiles in mouse and human embryonic stem cells (mESCs and hESCs) before and after differentiation to multiple lineages. We demonstrate that domains of coordinate replication ("replication domains") delineate distinct units of chromosomes with cell‐type specific boundaries. During differentiation, smaller discordantly replicating domains consolidate into larger coordinately replicated units. Moreover, induced pluripotent stem (iPS) re‐acquire the smaller replication domains of ESCs. When mESCs were followed through intermediate stages of differentiation, early to late (EtoL) replication changes preceded‐while late to early (LtoE) changes followed‐loss of pluripotency as measured by loss of Oct4 expression. However, changes in radial sub‐nuclear positioning, whether toward (EtoL) or away (LtoE) from the periphery, as well as replication domain consolidation, all took place during loss of pluripotency. We conclude that replication profiles can identify chromosome segments that undergo higher‐order organizational changes during major cell fate transitions. In particular, smaller replication domains and a higher density of timing transition regions define novel characteristics of the pluripotent state. Supported by NIH grants GM083337 and GM085354.