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Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells

Pradhan, Sunil Kumar ; Lozoya, Teresa ; Prorok, Paulina ; Yuan, Yue ; Lehmkuhl, Anne ; Zhang, Peng ; Cardoso, M. Cristina (2024)
Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells.
In: Genes, 2024, 15 (3)
doi: 10.26083/tuprints-00027162
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Item Type: Article
Type of entry: Secondary publication
Title: Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells
Language: English
Date: 14 May 2024
Place of Publication: Darmstadt
Year of primary publication: 27 February 2024
Place of primary publication: Basel
Publisher: MDPI
Journal or Publication Title: Genes
Volume of the journal: 15
Issue Number: 3
Collation: 26 Seiten
DOI: 10.26083/tuprints-00027162
Corresponding Links:
Origin: Secondary publication DeepGreen
Abstract:

DNA replication is a fundamental process ensuring the maintenance of the genome each time cells divide. This is particularly relevant early in development when cells divide profusely, later giving rise to entire organs. Here, we analyze and compare the genome replication progression in human embryonic stem cells, induced pluripotent stem cells, and differentiated cells. Using single-cell microscopic approaches, we map the spatio-temporal genome replication as a function of chromatin marks/compaction level. Furthermore, we mapped the replication timing of subchromosomal tandem repeat regions and interspersed repeat sequence elements. Albeit the majority of these genomic repeats did not change their replication timing from pluripotent to differentiated cells, we found developmental changes in the replication timing of rDNA repeats. Comparing single-cell super-resolution microscopic data with data from genome-wide sequencing approaches showed comparable numbers of replicons and large overlap in origins numbers and genomic location among developmental states with a generally higher origin variability in pluripotent cells. Using ratiometric analysis of incorporated nucleotides normalized per replisome in single cells, we uncovered differences in fork speed throughout the S phase in pluripotent cells but not in somatic cells. Altogether, our data define similarities and differences on the replication program and characteristics in human cells at different developmental states.

Uncontrolled Keywords: human cells, induced pluripotent stem cells, pluripotent embryonic stem cells, genome replication progression, repli-FISH, rDNA, centromere, chromatin compaction
Identification Number: Artikel-ID: 305
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-271629
Additional Information:

This article belongs to the Special Issue Mechanisms and Regulation of Human DNA Replication

Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 14 May 2024 13:35
Last Modified: 23 Sep 2024 06:17
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/27162
PPN: 521639875
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