PubMed:22613812
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/22613812","sourcedb":"PubMed","sourceid":"22613812","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/22613812","text":"Regulation of developmental competence and commitment towards the definitive endoderm lineage in human embryonic stem cells.\nHuman embryonic stem cells (hESCs) can self-renew and become all three germ layers. Nodal/Activin signaling specifies developmental status in hESCs: moderate Nodal/Activin signaling maintains pluripotency, while enhancement and inhibition promote definitive endoderm (DE) and neuroectoderm (NE) development, respectively. However, how modulation of Nodal/Activin signaling influences developmental competence and commitment toward specific lineages is still unclear. Here, we showed that enhancement of Nodal/Activin signaling for 4 days was necessary and sufficient to upregulate DE markers, while it diminished the upregulation of NE markers by inhibition of Nodal/Activin signaling. This suggests that after 4 days of enhanced Nodal/Activin signaling, hESCs are committed to the DE lineage and have lost competence toward the NE lineage. In contrast, inhibition of Nodal/Activin signaling using LY364947 for 2 days was sufficient to impair competence toward the DE lineage, although cells were still able to activate LEFTY1 and NODAL, direct targets of Nodal/Activin signaling. Expression analyses indicated that the levels of pluripotency regulators NANOG and POU5F1 were significantly diminished by 2 days of LY364947 treatment, although the expression of NANOG, but not POU5F1, was restored immediately upon Activin A treatment. Thus, downregulation of POU5F1 coincided with the abrogation of DE competence caused by inhibition of Nodal/Activin signaling.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_22613812_1_0","span":{"begin":125,"end":151},"obj":"expanded"},{"id":"SS2_22613812_1_0","span":{"begin":153,"end":158},"obj":"abbr"},{"id":"SS1_22613812_2_0","span":{"begin":372,"end":391},"obj":"expanded"},{"id":"SS2_22613812_2_0","span":{"begin":393,"end":395},"obj":"abbr"},{"id":"SS1_22613812_2_1","span":{"begin":401,"end":414},"obj":"expanded"},{"id":"SS2_22613812_2_1","span":{"begin":416,"end":418},"obj":"abbr"}],"relations":[{"id":"AE1_22613812_1_0","pred":"abbreviatedTo","subj":"SS1_22613812_1_0","obj":"SS2_22613812_1_0"},{"id":"AE1_22613812_2_0","pred":"abbreviatedTo","subj":"SS1_22613812_2_0","obj":"SS2_22613812_2_0"},{"id":"AE1_22613812_2_1","pred":"abbreviatedTo","subj":"SS1_22613812_2_1","obj":"SS2_22613812_2_1"}],"attributes":[{"subj":"SS1_22613812_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_22613812_1_0","pred":"source","obj":"Allie"},{"subj":"SS1_22613812_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_22613812_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_22613812_2_1","pred":"source","obj":"Allie"},{"subj":"SS2_22613812_2_1","pred":"source","obj":"Allie"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#ecac93","default":true}]}]}}