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Peer-reviewedCC BYScience Advances

Endogenous retrovirus control of calbindin is essential for human early embryogenesis

  • Judith Pape1
  • Afshan McCarthy2
  • Eduardo Serna-Morales3,4
  • Borzo Gharibi5
  • Tobias Plowman1
  • Elias Copin5
  • Rachael Thompson1
  • Laura Doglio1
  • Ruta Meleckyte-Martinez6
  • Lyn Healy6
  • Sara Tamagno6
  • Alberto Elosegui-Artola3,4
3 more authors
  • Silvia D. M. Santos5
  • Kathy K. Niakan2,7,8,9
  • George Kassiotis1,10
10 affiliations
  1. 1Retroviral Immunology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  2. 2Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  3. 3Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  4. 4Department of Physics, King’s College London, London, UK.
  5. 5Quantitative Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  6. 6Stem Cells and Organoids Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  7. 7Loke Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
  8. 8Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  9. 9Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
  10. 10Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.
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Abstract

The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non–small cell lung cancer optimal growth requires cancer cell–intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1 , encoding calbindin, is also observed in human embryonic stem cells (ESCs), but its significance remained uncertain. Here, we show that HERVH integration on 8q21.3 during Homininae evolution coincides with acquisition of expression of CALB1 in preimplantation embryos. We further show that CALB1 expression is critical for human ESC growth and the prevention of cellular senescence and for the formation of ESC-derived preimplantation blastoids and postgastrulation amnioids. Thus, the co-option of HERVH 8q21.3 cis-regulatory activity in lung cancer may echo its essential requirement for human embryo development.

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Cite

BibTeXRIS
BibTeX
@article{pape2026endogenous,
  title = {{Endogenous retrovirus control of calbindin is essential for human early embryogenesis}},
  author = {Judith Pape and Afshan McCarthy and Eduardo Serna-Morales and Borzo Gharibi and Tobias Plowman and Elias Copin and Rachael Thompson and Laura Doglio and Ruta Meleckyte-Martinez and Lyn Healy and Sara Tamagno and Alberto Elosegui-Artola and Silvia D. M. Santos and Kathy K. Niakan and George Kassiotis},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aee4523},
  url = {https://www.science.org/doi/10.1126/sciadv.aee4523},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Endogenous retrovirus control of calbindin is essential for human early embryogenesis
AU  - Judith Pape
AU  - Afshan McCarthy
AU  - Eduardo Serna-Morales
AU  - Borzo Gharibi
AU  - Tobias Plowman
AU  - Elias Copin
AU  - Rachael Thompson
AU  - Laura Doglio
AU  - Ruta Meleckyte-Martinez
AU  - Lyn Healy
AU  - Sara Tamagno
AU  - Alberto Elosegui-Artola
AU  - Silvia D. M. Santos
AU  - Kathy K. Niakan
AU  - George Kassiotis
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aee4523
UR  - https://www.science.org/doi/10.1126/sciadv.aee4523
AB  - The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non–small cell lung cancer optimal growth requires cancer cell–intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1 , encoding calbindin, is also observed in human embryonic stem cells (ESCs), but its significance remained uncertain. Here, we show that HERVH integration on 8q21.3 during Homininae evolution coincides with acquisition of expression of CALB1 in preimplantation embryos. We further show that CALB1 expression is critical for human ESC growth and the prevention of cellular senescence and for the formation of ESC-derived preimplantation blastoids and postgastrulation amnioids. Thus, the co-option of HERVH 8q21.3 cis-regulatory activity in lung cancer may echo its essential requirement for human embryo development.
SN  - 2375-2548
ER  -