Chromatin remodeling is restricted by transient GATA6 binding during iPSC differentiation to definitive endoderm

Efficient and scalable generation of primordial germ cells in 2D culture using basement membrane extract overlay

“…When treated with 10ng/ml of BMP4 and 10ng/ml ActA in the presence of BME overlay, D2 progenitors upregulated EOMES considerably, whereas inhibition of endogenous TGFβ/ActA signaling blocked EOMES expression (Figure 4D, 4E), indicating that EOMES is strongly regulated by ActA signaling in our culture system. Interestingly, treatment with a combination of BMP4 and ActA from D1-D3 with BME overlay resulted at D5 in the induction of SOX17+FOXA2+ cells (Figure S4G), presumably endoderm, which is consistent with the role of ActA and its target EOMES in endoderm differentiation (Heslop et al, 2022; Yoney et al, 2022).…”

“…Downstream of BMP4, BME-treated hPSCs showed increased pSMAD1/5/9, leading to upregulation of GATA3, TFAP2A, CDX2, and indirectly of EOMES. EOMES is essential for hPGCLC formation (Kobayashi et al ., 2017; Kojima et al ., 2017), but its continued and high expression has been shown to promote differentiation to endoderm (Heslop et al ., 2022; Yoney et al ., 2022). Consistent with this, EOMES is moderately expressed in D2-progenitor cells exposed to the BME overlay.…”

Efficient and Scalable Generation of Primordial Germ Cells in 2D Culture Using Basement Membrane Extract Overlay

“…EOMES is essential for hPGCLC formation, 6,19 but its continuous and high expression has been shown to promote differentiation to endoderm. 26,27 Consistent with this, EOMES is moderately expressed in day 2 progenitor cells exposed to the BMEx overlay. Moreover, in agreement with EOMES being a direct target of TGF-b/ ActA signaling, the addition of ActA increases EOMES expression, resulting in a reduction in hPGCLC yield and a shift toward differentiation to SOX17+/FOXA2+ endoderm-like cells.…”

“…Interestingly, treatment with a combination of BMP4 and ActA from day 1 to 3 with BMEx overlay resulted at day 5 in the induction of SOX17+-FOXA2+ cells (Figure S4G), presumably endoderm, which is consistent with the role of ActA and its target EOMES in endoderm differentiation. 26,27 Blocking endogenous TGF-b/ActA signaling from day 1 to 3, on the other hand, resulted in generation of mainly amniotic ectoderm cells at day 5, expressing markers such as TFAP2A, KRT7, HAND1, and GATA3 (Figure S4H).…”

How Chromatin Motor Complexes Influence the Nuclear Architecture: A Review of Chromatin Organization, Cohesins, and Condensins with a Focus on C. elegans

“…Members of this family use their highly conserved basic-leucine zipper domain to both bind DNA and dimerize with other members of the same family or even other transcription factors to bring segments of DNA together by bending the DNA strands physically [12]. These chromatin-organizing events are often transient [13]. Some transcription factors, like those in the WNT signaling family are sequestered in the cytoplasm until circumstances are reached that promote them to DNA 2024, 4 translocate into the nucleus [14].…”