Bmp4-induced differentiation of EpiSCs depends on Wnt signals
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62205 | GEO | 2014/12/24
SECONDARY ACCESSION(S): PRJNA263473
REPOSITORIES: GEO
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Project description:We used RNA-Seq to analyse the interactions between Bmp4 and Wnt at a genome-wide level in EpiSCs treated for 48 hrs with Bmp4 and/or Wnt3a in the presence of Activin and bFGF. Control EpiSC were cultured in the presence of IWP2 for 48h. Cells were cultured with BMP4 with or without IWP2; Wnt3a and Wnt3a with BMP4 for 48h.
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Project description:Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, which laid a foundation for studying the activation mechanism of qNSCs.
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Project description:MIXL1-GFP reporter lines were differentiated as Spin EBs in APEL medium supplemented with Wnt3a alone, BMP4 alone or Wnt3a/BMP4 in combination. EBs induced in the absence of growth factors were used as control. EBs induced with BMP4 or Wnt3a/BMP4 were FACS sorted based on E-CADHERIN and GFP expression. Unsorted EBs and sorted fractions were subjected to Illumina microarray processing.
2010-01-06 | E-MEXP-2495 | biostudies-arrayexpress
Project description:This microarray was performed to gain insight in the effect of GY118F stimulation in EpiSCs. This array is part of the following paper to be published in Nature Communications: “JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naïve pluripotency” by Anouk L. van Oosten, Yael Costa, Austin Smith & José C.R. Silva Gy0 a, gy0 b, gy0 c (triplicate samples for GY118F EpiSCs in N2B27+Activin+Fgf) c0 a, c0 b, c0 c (triplicate samples for Control EpiSCs in N2B27+Activin+Fgf) gy3 b, gy3 c (duplicate samples for GY118F EpiSCs in N2B27+Activin+Fgf stimulated with GCSF for 3 hours) c3 a, c3 b, c3 c (triplicate samples for Control EpiSCs in N2B27+Activin+Fgf stimulated with GCSF for 3 hours) Within the manucript genes of interest were defined as those that were significantly upregulated (P<0.01) above a 1.4 fold change threshold in GCSF stimulated GY118F EpiSCs as compared to those not stimulated, but for which the expression did not significantly change upon GCSF stimulation in the control. The fold change in expression was calculated by 2^absolute value of subtracted normalised data.
2012-04-30 | E-GEOD-36817 | biostudies-arrayexpress
Project description:This study describes the transcriptome profiling of: 1) mouse ES cells in LIF/KSR medium; 2)EpiSCs in bFGF/serum-free (KSR) medium; 3) EpiSCs treated with MM401/LIF KSR at D3 and D6 (P2); 4) rES reverted form EpiSC by MM401/LIF KSR treatment at P6, P30 with or without MM401 .
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Project description:Human embryonic stem cells (HESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. Here, we show that combining a second related ligand, BMP4, in combination with Activin A yields 15 to 20% more DE as compared to Activin A alone. The addition of recombinant BMP4 accelerates the downregulation of pluripotency factors, particularly SOX2, and results in upregulation of endogenous BMP2 and BMP4, which in turn leads to elevated levels of phospho-SMAD1/5/8 over the next three days of differentiation. Combined Activin A and BMP4 treatment also leads to an increase in the expression of DE genes CXCR4, SOX17 and FOXA2 when compared to Activin A addition alone. Comparative microarray studies between DE cells harvested on day 3 of differentiation further reveal a novel set of genes upregulated in response to initial BMP4 exposure. Several of these, including APLNR, LRIG3, MCC and LZTS1, are expressed either in the mouse primitive streak, the site of DE formation, or in nascent DE itself. Thus, this synergism between Activin A and BMP4 during the in vitro differentiation of HESC into DE suggests a complex interplay between BMP and Activin/Nodal signaling during the in vivo allocation and expansion of the endoderm lineage. 3 biological replicates of 3-day ActivinA treated HES3 human stem cell culture were compared to 3-day ActivinA+Bmp4 treated HES3 human stem cell culture and observed for differential genes expression
2011-11-10 | E-GEOD-30630 | biostudies-arrayexpress
Project description:Human embryonic stem cells (HESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. Here, we show that combining a second related ligand, BMP4, in combination with Activin A yields 15 to 20% more DE as compared to Activin A alone. The addition of recombinant BMP4 accelerates the downregulation of pluripotency factors, particularly SOX2, and results in upregulation of endogenous BMP2 and BMP4, which in turn leads to elevated levels of phospho-SMAD1/5/8 over the next three days of differentiation. Combined Activin A and BMP4 treatment also leads to an increase in the expression of DE genes CXCR4, SOX17 and FOXA2 when compared to Activin A addition alone. Comparative microarray studies between DE cells harvested on day 3 of differentiation further reveal a novel set of genes upregulated in response to initial BMP4 exposure. Several of these, including APLNR, LRIG3, MCC and LZTS1, are expressed either in the mouse primitive streak, the site of DE formation, or in nascent DE itself. Thus, this synergism between Activin A and BMP4 during the in vitro differentiation of HESC into DE suggests a complex interplay between BMP and Activin/Nodal signaling during the in vivo allocation and expansion of the endoderm lineage.
2011-11-10 | GSE30630 | GEO
Project description:Mouse naive and primed pluripotent stem cells, ESC and EpiSC, represent two distinct stages of pluripotency. Here we report that BMP4 drives primed to naive transition or PNT by reprogramming chromatin accessibility. ATAC-seq reveals that a short pulse of BMP4 triggers EpiSCs to close 26409 and open 6428 loci to reach an intermediate state that continue to open 18744 and close 7042 loci under 2iL until reaching a naive state, following with a dramatic reactivation of the silenced X chromosome. Among loci opened by BMP4 are those encoding Id1, Tfap2c/2a and Zbtb7b that synergistically drive PNT without BMP4. Tfap2c-/- ESCs or EpiSCs self-renew normally, while the former capable of differentiating to the latter but the latter fails to undergo PNT, a defect rescuable by exogenous Tfap2c. Our results link BMP4 to PNT through a binary logic of chromatin closing and opening, revealing the intrinsic power of extracellular factors to reorganize nuclear architecture in development.
2020-06-16 | GSE122936 | GEO
Project description:Mouse naive and primed pluripotent stem cells, ESC and EpiSC, represent two distinct stages of pluripotency. Here we report that BMP4 drives primed to naive transition or PNT by reprogramming chromatin accessibility. ATAC-seq reveals that a short pulse of BMP4 triggers EpiSCs to close 26409 and open 6428 loci to reach an intermediate state that continue to open 18744 and close 7042 loci under 2iL until reaching a naive state, following with a dramatic reactivation of the silenced X chromosome. Among loci opened by BMP4 are those encoding Id1, Tfap2c/2a and Zbtb7b that synergistically drive PNT without BMP4. Tfap2c-/- ESCs or EpiSCs self-renew normally, while the former capable of differentiating to the latter but the latter fails to undergo PNT, a defect rescuable by exogenous Tfap2c. Our results link BMP4 to PNT through a binary logic of chromatin closing and opening, revealing the intrinsic power of extracellular factors to reorganize nuclear architecture in development.
2020-06-16 | GSE122935 | GEO
Project description:Bone morphogenetic protein (BMP) signaling is known to support differentiation of human embryonic stem cells (hESCs) into mesoderm and extraembryonic lineages, whereas other signaling pathways can largely influence this lineage specification. Here, we set out to reinvestigate the influence of ACTIVIN/NODAL and fibroblast growth factor (FGF) pathways on the lineage choices made by hESCs during BMP4-driven differentiation. We show that BMP activation, coupled with inhibition of both ACTIVIN/NODAL and FGF signaling, induces differentiation of hESCs, specifically to M-NM-2hCG hormone-secreting multinucleated syncytiotrophoblast and does not support induction of embryonic and extraembryonic lineages, extravillous trophoblast, and primitive endoderm. It has been previously reported that FGF2 can switch BMP4-induced hESC differentiation outcome to mesendoderm. Here, we show that FGF inhibition alone, or in combination with either ACTIVIN/NODAL inhibition or BMP activation, supports hESC differentiation to hCG-secreting syncytiotrophoblast. We show that the inhibition of the FGF pathway acts as a key in directing BMP4-mediated hESC differentiation to syncytiotrophoblast. Human embryonic Stem Cells (hESCs) were treated under defined conditions (N2B27) with BMP4 (B), SB431542 (SB) (ACTIVIN/NODAL inhibitor), SU5402 (SU) (FGFR1 inhibitor), FGF2 (F) either alone or in various combinations as mentioned, followed by isolation of total RNA.
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