Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts

Tao Bai; Chian Yu Peng; Ivy Aneas; Noboru Sakabe; Daniela F. Requena; Christine Billstrand; Marcelo Nobrega; Carole Ober; Mana Parast; John A. Kessler

doi:10.1016/j.scr.2021.102507

Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts

Tao Bai, Chian Yu Peng, Ivy Aneas, Noboru Sakabe, Daniela F. Requena, Christine Billstrand, Marcelo Nobrega, Carole Ober, Mana Parast, John A. Kessler^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Human trophoblast stem cells (hTSC) can be isolated from first trimester placenta but not from term placenta. Here we demonstrate that villous cytotrophoblasts (vCTB) from term placenta can be reprogrammed into induced trophoblastic stem-like cells (iTSC) by introducing sets of transcription factors. The iTSCs express TSC markers such as GATA3, TEAD4 and ELF5, and are multipotent, validated by their differentiation into both extravillous trophoblasts (EVT) and syncytiotrophoblasts (STB) in vitro and in vivo. The iTSC can be passaged indefinitely in vitro without slowing of growth. The transcriptome profile of these cells closely resembles the profile of hTSC isolated from first trimester placentae but different from the term placental vCTB from which they originated. The ability to reprogram cells from term placenta into iTSC will allow study of early gestation events which impact placental function later in gestation, including preeclampsia and spontaneous preterm birth.

Original language	English (US)
Article number	102507
Journal	Stem Cell Research
Volume	56
DOIs	https://doi.org/10.1016/j.scr.2021.102507
State	Published - Oct 2021

Funding

This work was supported by funding from the National Institute of Child Health and Human Development under award number R01-HD089537 (MMP and DFR).

Keywords

Differentiation
Placenta
Reprogramming
Stem cell
Trophoblast

ASJC Scopus subject areas

Cell Biology
Developmental Biology

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10.1016/j.scr.2021.102507

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title = "Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts",

abstract = "Human trophoblast stem cells (hTSC) can be isolated from first trimester placenta but not from term placenta. Here we demonstrate that villous cytotrophoblasts (vCTB) from term placenta can be reprogrammed into induced trophoblastic stem-like cells (iTSC) by introducing sets of transcription factors. The iTSCs express TSC markers such as GATA3, TEAD4 and ELF5, and are multipotent, validated by their differentiation into both extravillous trophoblasts (EVT) and syncytiotrophoblasts (STB) in vitro and in vivo. The iTSC can be passaged indefinitely in vitro without slowing of growth. The transcriptome profile of these cells closely resembles the profile of hTSC isolated from first trimester placentae but different from the term placental vCTB from which they originated. The ability to reprogram cells from term placenta into iTSC will allow study of early gestation events which impact placental function later in gestation, including preeclampsia and spontaneous preterm birth.",

keywords = "Differentiation, Placenta, Reprogramming, Stem cell, Trophoblast",

author = "Tao Bai and Peng, {Chian Yu} and Ivy Aneas and Noboru Sakabe and Requena, {Daniela F.} and Christine Billstrand and Marcelo Nobrega and Carole Ober and Mana Parast and Kessler, {John A.}",

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year = "2021",

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doi = "10.1016/j.scr.2021.102507",

language = "English (US)",

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journal = "Stem Cell Research",

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T1 - Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts

AU - Bai, Tao

AU - Peng, Chian Yu

AU - Aneas, Ivy

AU - Sakabe, Noboru

AU - Requena, Daniela F.

AU - Billstrand, Christine

AU - Nobrega, Marcelo

AU - Ober, Carole

AU - Parast, Mana

AU - Kessler, John A.

PY - 2021/10

Y1 - 2021/10

N2 - Human trophoblast stem cells (hTSC) can be isolated from first trimester placenta but not from term placenta. Here we demonstrate that villous cytotrophoblasts (vCTB) from term placenta can be reprogrammed into induced trophoblastic stem-like cells (iTSC) by introducing sets of transcription factors. The iTSCs express TSC markers such as GATA3, TEAD4 and ELF5, and are multipotent, validated by their differentiation into both extravillous trophoblasts (EVT) and syncytiotrophoblasts (STB) in vitro and in vivo. The iTSC can be passaged indefinitely in vitro without slowing of growth. The transcriptome profile of these cells closely resembles the profile of hTSC isolated from first trimester placentae but different from the term placental vCTB from which they originated. The ability to reprogram cells from term placenta into iTSC will allow study of early gestation events which impact placental function later in gestation, including preeclampsia and spontaneous preterm birth.

AB - Human trophoblast stem cells (hTSC) can be isolated from first trimester placenta but not from term placenta. Here we demonstrate that villous cytotrophoblasts (vCTB) from term placenta can be reprogrammed into induced trophoblastic stem-like cells (iTSC) by introducing sets of transcription factors. The iTSCs express TSC markers such as GATA3, TEAD4 and ELF5, and are multipotent, validated by their differentiation into both extravillous trophoblasts (EVT) and syncytiotrophoblasts (STB) in vitro and in vivo. The iTSC can be passaged indefinitely in vitro without slowing of growth. The transcriptome profile of these cells closely resembles the profile of hTSC isolated from first trimester placentae but different from the term placental vCTB from which they originated. The ability to reprogram cells from term placenta into iTSC will allow study of early gestation events which impact placental function later in gestation, including preeclampsia and spontaneous preterm birth.

KW - Differentiation

KW - Placenta

KW - Reprogramming

KW - Stem cell

KW - Trophoblast

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Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts

Abstract

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Keywords

ASJC Scopus subject areas

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