scholarly journals Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo

2021 ◽  
Author(s):  
Thomas A Carter ◽  
Manvendra Singh ◽  
Gabrijela Dumbovic ◽  
Jason Chobirko ◽  
John Rinn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Embryo ◽  
Expression Patterns ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Binding Motif ◽  
Sequence Evolution ◽  
Long Terminal Repeats ◽  
Transcription Factor Binding Motif

The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH elements achieve such transcriptional specificity remains poorly understood. To uncover the sequence features underlying HERVH transcriptional activity, we performed a phyloregulatory analysis of the long terminal repeats (LTR7) of the HERVH family, which harbor its promoter, using a wealth of regulatory genomics data. We found that the family includes at least 8 previously unrecognized subfamilies that have been active at different timepoints in primate evolution and display distinct expression patterns during human embryonic development. Notably, nearly all HERVH elements transcribed in ESCs belong to one of the youngest subfamilies we dubbed LTR7up. LTR7 sequence evolution was driven by complex mutational processes, including multiple recombination events between subfamilies, that led to transcription factor binding motif modules characteristic of each subfamily. Using a reporter assay, we show that one such motif, a predicted SOX2/3 binding site unique to LTR7up, is essential for robust promoter activity in induced pluripotent stem cells. Together these findings illuminate the mechanisms by which HERVH diversified its expression pattern during evolution to colonize distinct cellular niches within the human embryo.

scholarly journals Cell-autonomous differentiation of human primed embryonic stem cells into trophoblastic syncytia through the nascent amnion-like cell state

2021 ◽  
Author(s):  
Masatoshi Ohgushi ◽  
Mototsugu Eiraku
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Embryo ◽  
Embryonic Stem ◽  
Cell State ◽  
Transient Population ◽  
Post Implantation

Human primed embryonic stem cells (pESCs) are known to be converted to cells with several trophoblast properties, but it has remained controversial whether this phenomenon represents the inherent differentiation competence of human pESCs to trophoblast lineages. In this study, we report that chemical blockage of ACTIVIN/NODAL and FGF signals is sufficient to steer human pESCs into GATA3-expressing cells that give rise to hormone-producing syncytia analogous to syncytiotrophoblasts of the post-implantation stage of the human embryo. Taking advantage of this system, we identified two distinct modes of cell-autonomous genetic programs and their coordinated actions to initiate the differentiation. We also found a transient population reminiscent of nascent amnion and then a spontaneous branch of differentiation trajectory leading to syncytiotrophoblast-like syncytial cells. These results provide insights into the possible extraembryonic differentiation pathway that is unique in primate embryogenesis and is relevant to the trophoblast competence of human primed pluripotent stem cells.

scholarly journals Human Endogenous Retrovirus HERV-K14 Families: Status, Variants, Evolution, and Mobilization of Other Cellular Sequences

2005 ◽  
Vol 79 (5) ◽  
pp. 2941-2949 ◽  
Author(s):  
Aline Flockerzi ◽  
Stefan Burkhardt ◽  
Werner Schempp ◽  
Eckart Meese ◽  
Jens Mayer
Keyword(s):  
Human Genome ◽  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Long Terminal Repeats ◽  
Essential Information ◽  
Human Endogenous Retroviruses ◽  
Consensus Sequences

ABSTRACT The human genome harbors many distinct families of human endogenous retroviruses (HERVs) that stem from exogenous retroviruses that infected the germ line millions of years ago. Many HERV families remain to be investigated. We report in the present study the detailed characterization of the HERV-K14I and HERV-K14CI families as they are represented in the human genome. Most of the 68 HERV-K14I and 23 HERV-K14CI proviruses are severely mutated, frequently displaying uniform deletions of retroviral genes and long terminal repeats (LTRs). Both HERV families entered the germ line ∼39 million years ago, as evidenced by homologous sequences in hominoids and Old World primates and calculation of evolutionary ages based on a molecular clock. Proviruses of both families were formed during a brief period. A majority of HERV-K14CI proviruses on the Y chromosome mimic a higher evolutionary age, showing that LTR-LTR divergence data can indicate false ages. Fully translatable consensus sequences encoding major retroviral proteins were generated. Most HERV-K14I loci lack an env gene and are structurally reminiscent of LTR retrotransposons. A minority of HERV-K14I variants display an env gene. HERV-K14I proviruses are associated with three distinct LTR families, while HERV-K14CI is associated with a single LTR family. Hybrid proviruses consisting of HERV-K14I and HERV-W sequences that appear to have produced provirus progeny in the genome were detected. Several HERV-K14I proviruses harbor TRPC6 mRNA portions, exemplifying mobilization of cellular transcripts by HERVs. Our analysis contributes essential information on two more HERV families and on the biology of HERV sequences in general.

scholarly journals Cell cycle dynamics of human pluripotent stem cells primed for differentiation

2019 ◽  
Author(s):  
Anna Shcherbina ◽  
Jingling Li ◽  
Cyndhavi Narayanan ◽  
William Greenleaf ◽  
Anshul Kundaje ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Expression Patterns ◽  
Human Pluripotent Stem Cells ◽  
Specific Manner ◽  
A Cell ◽  
Cell Cycle Dynamics ◽  
Differentiation Gene ◽  
Cycle Indicator

Understanding the molecular properties of the cell cycle of human pluripotent stem cells (hPSCs) is critical for effectively promoting differentiation. Here, we use the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) system adapted into hPSCs and perform RNA-sequencing on cell cycle sorted hPSCs primed and unprimed for differentiation. Gene expression patterns of signaling factors and developmental regulators change in a cell cycle-specific manner in cells primed for differentiation without altering genes associated with pluripotency. Furthermore, we identify an important role for PI3K signaling in regulating the early transitory states of hPSCs towards differentiation.

Analysis of KAP1 expression patterns and human endogenous retrovirus Env proteins in ovarian cancer

2020 ◽  
Vol 42 (10) ◽  
pp. 1145-1150
Author(s):  
Kyung-Yoon Jeon ◽  
Eun-Ji Ko ◽  
Young Lim Oh ◽  
Hongbae Kim ◽  
Wan Kyu Eo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Expression Patterns ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals Expression Patterns of Non-Coding Spliced Transcripts from Human Endogenous Retrovirus HERV-H Elements in Colon Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e29950 ◽  
Author(s):  
Qiaoyi Liang ◽  
Zefeng Xu ◽  
Rongzhen Xu ◽  
Lijun Wu ◽  
Shu Zheng
Keyword(s):  
Colon Cancer ◽  
Expression Patterns ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals Expression Patterns of Cancer-Testis Antigens in Human Embryonic Stem Cells and Their Cell Derivatives Indicate Lineage Tracks

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Nadya Lifantseva ◽  
Anna Koltsova ◽  
Tatyana Krylova ◽  
Tatyana Yakovleva ◽  
Galina Poljanskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pluripotent Stem Cells ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Cancer Cell Lines ◽  
Cancer Testis Antigens ◽  
Hes Cells ◽  
Cancer Testis

Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES cells and embryoid body cells expressed MAGE-A3, -A6, -A4, -A8, and GAGEs while later differentiated derivatives expressed only MAGE-A8 or MAGE-A4. Likewise, mouse pluripotent stem cells also express CTAs of Magea but not Mageb family. Despite similarity of the hES and hEC cell expression patterns, MAGE-A2 and MAGE-B2 were detected only in hEC cells but not in hES cells. Moreover, our analysis has shown that CTAs are aberrantly expressed in cancer cell lines and display low tissue specificity. The identification of CTA expression patterns in pluripotent stem cells and their derivatives may be useful for isolation of abnormally CTA-expressing cells to improve the safety of stem-cell based therapy.

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