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Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility

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...

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Autores principales: Saatcioglu, Hatice Duygu, Kano, Motohiro, Horn, Heiko, Zhang, Lihua, Samore, Wesley, Nagykery, Nicholas, Meinsohn, Marie-Charlotte, Hyun, Minsuk, Suliman, Rana, Poulo, Joy, Hsu, Jennifer, Sacha, Caitlin, Wang, Dan, Gao, Guangping, Lage, Kasper, Oliva, Esther, Morris Sabatini, Mary E, Donahoe, Patricia K, Pépin, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650247/
https://www.ncbi.nlm.nih.gov/pubmed/31232694
http://dx.doi.org/10.7554/eLife.46349
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author Saatcioglu, Hatice Duygu
Kano, Motohiro
Horn, Heiko
Zhang, Lihua
Samore, Wesley
Nagykery, Nicholas
Meinsohn, Marie-Charlotte
Hyun, Minsuk
Suliman, Rana
Poulo, Joy
Hsu, Jennifer
Sacha, Caitlin
Wang, Dan
Gao, Guangping
Lage, Kasper
Oliva, Esther
Morris Sabatini, Mary E
Donahoe, Patricia K
Pépin, David
author_facet Saatcioglu, Hatice Duygu
Kano, Motohiro
Horn, Heiko
Zhang, Lihua
Samore, Wesley
Nagykery, Nicholas
Meinsohn, Marie-Charlotte
Hyun, Minsuk
Suliman, Rana
Poulo, Joy
Hsu, Jennifer
Sacha, Caitlin
Wang, Dan
Gao, Guangping
Lage, Kasper
Oliva, Esther
Morris Sabatini, Mary E
Donahoe, Patricia K
Pépin, David
author_sort Saatcioglu, Hatice Duygu
collection PubMed
description 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.
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spelling pubmed-66502472019-07-24 Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility Saatcioglu, Hatice Duygu Kano, Motohiro Horn, Heiko Zhang, Lihua Samore, Wesley Nagykery, Nicholas Meinsohn, Marie-Charlotte Hyun, Minsuk Suliman, Rana Poulo, Joy Hsu, Jennifer Sacha, Caitlin Wang, Dan Gao, Guangping Lage, Kasper Oliva, Esther Morris Sabatini, Mary E Donahoe, Patricia K Pépin, David eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2019-06-24 /pmc/articles/PMC6650247/ /pubmed/31232694 http://dx.doi.org/10.7554/eLife.46349 Text en © 2019, Saatcioglu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Saatcioglu, Hatice Duygu
Kano, Motohiro
Horn, Heiko
Zhang, Lihua
Samore, Wesley
Nagykery, Nicholas
Meinsohn, Marie-Charlotte
Hyun, Minsuk
Suliman, Rana
Poulo, Joy
Hsu, Jennifer
Sacha, Caitlin
Wang, Dan
Gao, Guangping
Lage, Kasper
Oliva, Esther
Morris Sabatini, Mary E
Donahoe, Patricia K
Pépin, David
Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title_full Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title_fullStr Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title_full_unstemmed Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title_short Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility
title_sort single-cell sequencing of neonatal uterus reveals an misr2+ endometrial progenitor indispensable for fertility
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650247/
https://www.ncbi.nlm.nih.gov/pubmed/31232694
http://dx.doi.org/10.7554/eLife.46349
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