Genome editing reveals a role for OCT4 in human embryogenesis

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Genome editing in human zygotes shows that OCT4 is required for normal development at an earlier stage in humans than in mice.

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featureCounts: An efficient general-purpose program for assigning sequence reads to genomic features

, , (2013)

Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages.

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Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.

J. Nichols, B Zevnik, K Anastassiadis … (1998)

Oct4 is a mammalian POU transcription factor expressed by early embryo cells and germ cells. We report that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo. Oct4-deficient embryos develop to the blastocyst stage, but the inner cell mass cells are not pluripotent. Instead, they are restricted to differentiation along the extraembryonic trophoblast lineage. Furthermore, in the absence of a true inner cell mass, trophoblast proliferation is not maintained in Oct4-/- embryos. Expansion of trophoblast precursors is restored, however, by an Oct4 target gene product, fibroblast growth factor-4. Therefore, Oct4 also determines paracrine growth factor signaling from stem cells to the trophectoderm.

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Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage.

Connie Wong, Kevin E. Loewke, Nancy L. Bossert … (2010)

We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.

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DOI:: 10.1038/nature24033

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Genome editing reveals a role for OCT4 in human embryogenesis

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Genome Integrity

Most cited references 26

featureCounts: An efficient general-purpose program for assigning sequence reads to genomic features

Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.

Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage.

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