The GATA transcriptional program dictates cell fate equilibrium to establish the maternal-fetal exchange interface and fetal development
The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal-fetal exchange interface.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 8 vom: 20. Feb., Seite e2310502121 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ghosh, Ananya [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
GATA Transcription Factors |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 28.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2310502121 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368363260 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368363260 | ||
| 003 | DE-627 | ||
| 005 | 20240229170948.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240213s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2310502121 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1310.xml |
| 035 | |a (DE-627)NLM368363260 | ||
| 035 | |a (NLM)38346193 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ghosh, Ananya |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The GATA transcriptional program dictates cell fate equilibrium to establish the maternal-fetal exchange interface and fetal development |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 28.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal-fetal exchange interface | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GATA2 | |
| 650 | 4 | |a GATA3 | |
| 650 | 4 | |a placenta | |
| 650 | 4 | |a syncytiotrophoblast | |
| 650 | 4 | |a trophoblast progenitors | |
| 650 | 7 | |a GATA Transcription Factors |2 NLM | |
| 700 | 1 | |a Kumar, Rajnish |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Ram P |e verfasserin |4 aut | |
| 700 | 1 | |a Ray, Soma |e verfasserin |4 aut | |
| 700 | 1 | |a Saha, Abhik |e verfasserin |4 aut | |
| 700 | 1 | |a Roy, Namrata |e verfasserin |4 aut | |
| 700 | 1 | |a Dasgupta, Purbasa |e verfasserin |4 aut | |
| 700 | 1 | |a Marsh, Courtney |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Soumen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 121(2024), 8 vom: 20. Feb., Seite e2310502121 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:121 |g year:2024 |g number:8 |g day:20 |g month:02 |g pages:e2310502121 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2310502121 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 121 |j 2024 |e 8 |b 20 |c 02 |h e2310502121 | ||