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Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis
Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. Prior work suggested that TPM1 regulated blood cell formation in vitro, but it was unclear how or when TPM1...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491315/ https://www.ncbi.nlm.nih.gov/pubmed/37693628 http://dx.doi.org/10.1101/2023.09.01.555861 |
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author | Wilken, Madison B Fonar, Gennadiy Nations, Catriana Pavani, Giulia Tsao, Victor Garifallou, James Tober, Joanna Bennett, Laura Maguire, Jean Ann Gagne, Alyssa Okoli, Nkemdilim Gadue, Paul Chou, Stella T Speck, Nancy A French, Deborah L Thom, Christopher S |
author_facet | Wilken, Madison B Fonar, Gennadiy Nations, Catriana Pavani, Giulia Tsao, Victor Garifallou, James Tober, Joanna Bennett, Laura Maguire, Jean Ann Gagne, Alyssa Okoli, Nkemdilim Gadue, Paul Chou, Stella T Speck, Nancy A French, Deborah L Thom, Christopher S |
author_sort | Wilken, Madison B |
collection | PubMed |
description | Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. Prior work suggested that TPM1 regulated blood cell formation in vitro, but it was unclear how or when TPM1 affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, TPM1 knockout was found to augment developmental cell state transitions, as well as TNFα and GTPase signaling pathways, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses showed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects of TPM1 on developmental hematopoiesis. |
format | Online Article Text |
id | pubmed-10491315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104913152023-09-09 Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis Wilken, Madison B Fonar, Gennadiy Nations, Catriana Pavani, Giulia Tsao, Victor Garifallou, James Tober, Joanna Bennett, Laura Maguire, Jean Ann Gagne, Alyssa Okoli, Nkemdilim Gadue, Paul Chou, Stella T Speck, Nancy A French, Deborah L Thom, Christopher S bioRxiv Article Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. Prior work suggested that TPM1 regulated blood cell formation in vitro, but it was unclear how or when TPM1 affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, TPM1 knockout was found to augment developmental cell state transitions, as well as TNFα and GTPase signaling pathways, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses showed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects of TPM1 on developmental hematopoiesis. Cold Spring Harbor Laboratory 2023-09-02 /pmc/articles/PMC10491315/ /pubmed/37693628 http://dx.doi.org/10.1101/2023.09.01.555861 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Wilken, Madison B Fonar, Gennadiy Nations, Catriana Pavani, Giulia Tsao, Victor Garifallou, James Tober, Joanna Bennett, Laura Maguire, Jean Ann Gagne, Alyssa Okoli, Nkemdilim Gadue, Paul Chou, Stella T Speck, Nancy A French, Deborah L Thom, Christopher S Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title | Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title_full | Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title_fullStr | Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title_full_unstemmed | Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title_short | Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
title_sort | tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491315/ https://www.ncbi.nlm.nih.gov/pubmed/37693628 http://dx.doi.org/10.1101/2023.09.01.555861 |
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