Abstract
Human embryonic stem cells (hESCs) can be used to study the early events in human development and, hopefully, to understand how to differentiate human pluripotent cells for clinical use. To define how L3MBTL1, a chromatin-associated polycomb group protein with transcriptional repressive activities, regulates early events in embryonic cell differentiation, we created hESC lines that constitutively express shRNAs directed against L3MBTL1. The L3MBTL1 knockdown (KD) hESCs maintained normal morphology, proliferation, cell cycle kinetics, cell surface markers, and karyotype after 40 passages. However, under conditions that promote spontaneous differentiation, the L3MBTL1 KD cells differentiated into a relatively homogeneous population of large, flat trophoblast-like cells, unlike the multilineage differentiation seen with the control cells. The differentiated L3MBTL1 KD cells expressed numerous trophoblast markers and secreted placental hormones. Although the L3MBTL1 KD cells could be induced to differentiate into various embryonic lineages, they adopted an exclusive trophoblast fate during spontaneous differentiation. Our data demonstrate that depletion of L3MBTL1 does not affect hESC self-renewal, rather it enhances differentiation toward extra-embryonic trophoblast tissues.
| Original language | English |
|---|---|
| Pages (from-to) | 1889-1900 |
| Number of pages | 12 |
| Journal | Stem Cells and Development |
| Volume | 20 |
| Issue number | 11 |
| State | Published - Nov 1 2011 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Hematology
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L3MBTL1 deficiency directs the differentiation of human embryonic stem cells toward trophectoderm. / Hoya-Arias, Ruben; Tomishima, Mark; Perna, Fabiana; Voza, Francesca; Nimer, Stephen D.
In: Stem Cells and Development, Vol. 20, No. 11, 01.11.2011, p. 1889-1900.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - L3MBTL1 deficiency directs the differentiation of human embryonic stem cells toward trophectoderm.
AU - Hoya-Arias, Ruben
AU - Tomishima, Mark
AU - Perna, Fabiana
AU - Voza, Francesca
AU - Nimer, Stephen D
PY - 2011/11/1
Y1 - 2011/11/1
N2 - Human embryonic stem cells (hESCs) can be used to study the early events in human development and, hopefully, to understand how to differentiate human pluripotent cells for clinical use. To define how L3MBTL1, a chromatin-associated polycomb group protein with transcriptional repressive activities, regulates early events in embryonic cell differentiation, we created hESC lines that constitutively express shRNAs directed against L3MBTL1. The L3MBTL1 knockdown (KD) hESCs maintained normal morphology, proliferation, cell cycle kinetics, cell surface markers, and karyotype after 40 passages. However, under conditions that promote spontaneous differentiation, the L3MBTL1 KD cells differentiated into a relatively homogeneous population of large, flat trophoblast-like cells, unlike the multilineage differentiation seen with the control cells. The differentiated L3MBTL1 KD cells expressed numerous trophoblast markers and secreted placental hormones. Although the L3MBTL1 KD cells could be induced to differentiate into various embryonic lineages, they adopted an exclusive trophoblast fate during spontaneous differentiation. Our data demonstrate that depletion of L3MBTL1 does not affect hESC self-renewal, rather it enhances differentiation toward extra-embryonic trophoblast tissues.
AB - Human embryonic stem cells (hESCs) can be used to study the early events in human development and, hopefully, to understand how to differentiate human pluripotent cells for clinical use. To define how L3MBTL1, a chromatin-associated polycomb group protein with transcriptional repressive activities, regulates early events in embryonic cell differentiation, we created hESC lines that constitutively express shRNAs directed against L3MBTL1. The L3MBTL1 knockdown (KD) hESCs maintained normal morphology, proliferation, cell cycle kinetics, cell surface markers, and karyotype after 40 passages. However, under conditions that promote spontaneous differentiation, the L3MBTL1 KD cells differentiated into a relatively homogeneous population of large, flat trophoblast-like cells, unlike the multilineage differentiation seen with the control cells. The differentiated L3MBTL1 KD cells expressed numerous trophoblast markers and secreted placental hormones. Although the L3MBTL1 KD cells could be induced to differentiate into various embryonic lineages, they adopted an exclusive trophoblast fate during spontaneous differentiation. Our data demonstrate that depletion of L3MBTL1 does not affect hESC self-renewal, rather it enhances differentiation toward extra-embryonic trophoblast tissues.
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M3 - Article
C2 - 21341991
AN - SCOPUS:84857073112
VL - 20
SP - 1889
EP - 1900
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 11
ER -