Single-cell sequencing of neonatal uterus reveals an endometrial progenitor indispensable for fertility

Hd Saatcioglu, M. Kano, H. Horn, Lh H. Zhang, Wr R. Samore, N. Nagykery, Mc C. Meinsohn, M. Hyun, R. Suliman, Mp P. Joy, J. Hsu, C. Sacha, D. Wang, G. Gao, L. Kasper, E. Oliva, Me E. Morris Sabatini, Pk K. Donahoe, D. Pépin

Research output: Contribution to journalArticle

Abstract

The Mullerian ducts are the anlagen of the female reproductive tract, which regress in the male fetus in response to MIS. This process is driven by subluminal mesenchymal cells expressing Misr2, which trigger the regression of the adjacent Mullerian ductal epithelium. In females these Misr2+ cells are retained, yet their contribution to the development of the uterus remains unknown. Here, we report that subluminal Misr2+ cells persist postnatally in the uterus of rodents, but recede by week 37 of gestation in humans. Using single-cell RNA sequencing we demonstrate that ectopic postnatal MIS administration inhibits these cells and prevents the formation of endometrial stroma in rodents, suggesting a progenitor function. Exposure to MIS during the first six days of life, by inhibiting specification of the stroma, dysregulates paracrine signals necessary for uterine development, eventually resulting in apoptosis of the Misr2+ cells, uterine hypoplasia, and complete infertility in the adult female.

Original languageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - 2019 Jun 1
Externally publishedYes

Fingerprint

Management information systems
Uterus
Fertility
Ducts
Rodentia
Cells
RNA
Mullerian Ducts
Apoptosis
RNA Sequence Analysis
Specifications
Infertility
Fetus
Epithelium
Pregnancy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Single-cell sequencing of neonatal uterus reveals an endometrial progenitor indispensable for fertility. / Saatcioglu, Hd; Kano, M.; Horn, H.; Zhang, Lh H.; Samore, Wr R.; Nagykery, N.; Meinsohn, Mc C.; Hyun, M.; Suliman, R.; Joy, Mp P.; Hsu, J.; Sacha, C.; Wang, D.; Gao, G.; Kasper, L.; Oliva, E.; Morris Sabatini, Me E.; Donahoe, Pk K.; Pépin, D.

In: eLife, Vol. 8, 01.06.2019.

Research output: Contribution to journalArticle

Saatcioglu, H, Kano, M, Horn, H, Zhang, LH, Samore, WR, Nagykery, N, Meinsohn, MC, Hyun, M, Suliman, R, Joy, MP, Hsu, J, Sacha, C, Wang, D, Gao, G, Kasper, L, Oliva, E, Morris Sabatini, ME, Donahoe, PK & Pépin, D 2019, 'Single-cell sequencing of neonatal uterus reveals an endometrial progenitor indispensable for fertility', eLife, vol. 8. https://doi.org/10.7554/eLife.46349.001
Saatcioglu, Hd ; Kano, M. ; Horn, H. ; Zhang, Lh H. ; Samore, Wr R. ; Nagykery, N. ; Meinsohn, Mc C. ; Hyun, M. ; Suliman, R. ; Joy, Mp P. ; Hsu, J. ; Sacha, C. ; Wang, D. ; Gao, G. ; Kasper, L. ; Oliva, E. ; Morris Sabatini, Me E. ; Donahoe, Pk K. ; Pépin, D. / Single-cell sequencing of neonatal uterus reveals an endometrial progenitor indispensable for fertility. In: eLife. 2019 ; Vol. 8.
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