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Cell potency describes a cells capacity to differentiate into other cell types, with higher potency indicating greater plasticity. Generally, cell potency decreases as embryo development proceeds however this is not the case at the beginning of the process when, following fertilisation, a highly differentiated egg cell gives rise to ball of totipotent cells capable of\u00a0forming all the lineages of the embryo. In mammals the emergence of totipotency is intimately linked both to the maternal zygotic transition, in which awakening of the transcriptionally inactive zygotic genome is coupled with degradation of maternally inherited transcripts, and a\u00a0<\/span>dramatic epigenetic reprogramming of the embryo. A totipotent state is then retained through\u00a0<\/span>early cleavages until the morula stage when the embryo segregates into the placenta forming trophectoderm (TE) and foetus forming inner cell mass (ICM). A further decrease in potency is seen at the blastocyst stage when the inner cell mass splits into the primitive endoderm, which will give rise to the visceral endoderm and yolk sack and the pluripotent epiblast which will give rise to the foetus itself. Embryo implantation is accompanied by a further change in potency with the epiblast transitioning from a\u00a0na\u00efve state, away from differentiation to primed one, competent to respond to differentiation cues.\u00a0Both na\u00efve and primed stem cells can be derived from the embryo at pre and post implantation stages respectively and kept in culture.\u00a0Furthermore,\u00a0studies during the last decade have found that cultured embryonic stem cells (ESCs) regularly transition through a state that is similar to the 2-cell embryo and that this can be promoted through the use of various combinations of small molecules.\u00a0<\/span><\/p>\nThe overriding objective of my research is to uncover the mechanisms underlying mammalian totipotency and pluripotency acquisition and loss both in the embryo and in cell culture systems. To begin with we are focussing on the role of the Hippo signalling pathway in these processes which has been implicated in zygotic genome activation, trophectoderm formation and epiblast\/primitive endoderm segregation. For this we are making use of a wide variety of experimental approaches including CRISPR mediated\u00a0genome editing, high throughput sequencing, embryo micromanipulation and confocal imaging.<\/span><\/p>\n<\/div>\n\u00a0![\"\"](\"data:image\/svg+xml;base64,PHN2ZyB3aWR0aD0iMSIgaGVpZ2h0PSIxIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciPjwvc3ZnPg==\")
\u00a0<\/span><\/p>\n<\/div>\nCells at the edge of ES cell colonies have reduced expression of the pluripotency marker Nanog (green) and increased nuclear localisation of Yap1 (red).<\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n[\/et_pb_text][et_pb_divider _builder_version=”4.27.6″ _module_preset=”d057b755-ffa8-4fcd-923c-c94b7c9a9123″ hover_enabled=”0″ global_colors_info=”{%22gcid-primary-color%22:%91%22color%22%93}” show_divider=”off” sticky_enabled=”0″][\/et_pb_divider][et_pb_text _builder_version=”4.27.6″ _module_preset=”dc6ab383-11a3-454b-8ba1-6554be6042b4″ vertical_offset_tablet=”0″ horizontal_offset_tablet=”0″ hover_enabled=”0″ z_index_tablet=”0″ text_text_shadow_horizontal_length_tablet=”0px” text_text_shadow_vertical_length_tablet=”0px” text_text_shadow_blur_strength_tablet=”1px” link_text_shadow_horizontal_length_tablet=”0px” link_text_shadow_vertical_length_tablet=”0px” link_text_shadow_blur_strength_tablet=”1px” ul_text_shadow_horizontal_length_tablet=”0px” ul_text_shadow_vertical_length_tablet=”0px” ul_text_shadow_blur_strength_tablet=”1px” ol_text_shadow_horizontal_length_tablet=”0px” ol_text_shadow_vertical_length_tablet=”0px” ol_text_shadow_blur_strength_tablet=”1px” quote_text_shadow_horizontal_length_tablet=”0px” quote_text_shadow_vertical_length_tablet=”0px” quote_text_shadow_blur_strength_tablet=”1px” header_text_shadow_horizontal_length_tablet=”0px” header_text_shadow_vertical_length_tablet=”0px” header_text_shadow_blur_strength_tablet=”1px” header_2_text_shadow_horizontal_length_tablet=”0px” header_2_text_shadow_vertical_length_tablet=”0px” header_2_text_shadow_blur_strength_tablet=”1px” header_3_text_shadow_horizontal_length_tablet=”0px” header_3_text_shadow_vertical_length_tablet=”0px” header_3_text_shadow_blur_strength_tablet=”1px” header_4_text_shadow_horizontal_length_tablet=”0px” header_4_text_shadow_vertical_length_tablet=”0px” header_4_text_shadow_blur_strength_tablet=”1px” header_5_text_shadow_horizontal_length_tablet=”0px” header_5_text_shadow_vertical_length_tablet=”0px” header_5_text_shadow_blur_strength_tablet=”1px” header_6_text_shadow_horizontal_length_tablet=”0px” header_6_text_shadow_vertical_length_tablet=”0px” header_6_text_shadow_blur_strength_tablet=”1px” box_shadow_horizontal_tablet=”0px” box_shadow_vertical_tablet=”0px” box_shadow_blur_tablet=”40px” box_shadow_spread_tablet=”0px” global_colors_info=”{%22gcid-primary-color%22:%91%22header_text_color%22%93}” sticky_enabled=”0″]<\/p>\n
Relevant literature<\/h2>\n
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\n- Spruce T\u2020<\/u><\/strong>, Plass M, Gohr A, \u2026.., Pernaute B\u2020, Irimia M\u2020. (2022). The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians.\u00a0PLoS Biol<\/em>. 20(4): e3001615. doi: 10.1371\/journal.pbio.3001615.<\/li>\n
- Gentsch GE\u2020,\u00a0Spruce T<\/u><\/strong>, Owens NDL, Smith JC\u2020. (2019). Maternal pluripotency factors initiate extensive chromatin remodelling to predefine first response to inductive signals.\u00a0Nat Commun<\/em>. 19;10(1):4269. doi: 10.1038\/s41467-019-12263-w.<\/li>\n
- Gentsch GE*,\u00a0Spruce T*<\/u><\/strong>, Monteiro RS*, Owens NDL, Martin SR, Smith JC\u2020. (2018). Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus.\u00a0Dev Cell<\/em>. 12;44(5):597-610. doi: 10.1016\/j.devcel.2018.01.022.<\/li>\n
- Pernaute B,\u00a0Spruce T<\/u><\/strong>, Smith KM, S\u00e1nchez-Nieto JM, Manzanares M, Cobb B, Rodr\u00edguez TA\u2020. (2014). MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM.\u00a0Genes Dev<\/em>. 1;28(17):1873-8. doi: 10.1101\/gad.245621.114.<\/li>\n
- Spruce T*<\/u><\/strong>, Pernaute B*, Di-Gregorio A, Cobb B, Merkenschlager M, Manzanares M\u2020, Rodr\u00edguez TA\u2020 (2010). An early developmental role for miRNAs in the maintenance of extra-embryonic stem cells in the mouse embryo.\u00a0Dev Cell<\/em>.\u00a0<\/strong>19(2):207-219. doi: 10.1016\/j.devcel.2010.07.014.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n
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Lab members & collaborators<\/h2>\n
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Lab members<\/h3>\n
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Associated Investigator<\/h4>\n
Dr. Thomas Spruce, tspr1@upo.es<\/a><\/p>\n\n
Masters student<\/h4>\n
Marta Escobar<\/p>\n
<\/p>\n
Collaborators<\/h3>\n
\u00a0Dr. B\u00e1rbara Pernaute (CABD, Sevilla)<\/p>\n
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Genome DynamicsCell Potency Transitions Dr. Thomas Spruce \u00a0ResearcherSummary Cell potency describes a cells capacity to differentiate into other cell types, with higher potency indicating greater plasticity. Generally, cell potency […]<\/p>\n","protected":false},"author":3009,"featured_media":0,"parent":21588,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-20627","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/pages\/20627","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/users\/3009"}],"replies":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/comments?post=20627"}],"version-history":[{"count":7,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/pages\/20627\/revisions"}],"predecessor-version":[{"id":24342,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/pages\/20627\/revisions\/24342"}],"up":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/pages\/21588"}],"wp:attachment":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/media?parent=20627"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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\u00a0<\/span><\/p>\n<\/div>\n