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Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis

Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal H...

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Autores principales: Wang, Dahai, Tanaka-Yano, Mayuri, Meader, Eleanor, Kinney, Melissa A., Morris, Vivian, Lummertz da Rocha, Edroaldo, Liu, Nan, Liu, Tianxin, Zhu, Qian, Orkin, Stuart H., North, Trista E., Daley, George Q., Rowe, R. Grant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029260/
https://www.ncbi.nlm.nih.gov/pubmed/35385744
http://dx.doi.org/10.1016/j.celrep.2022.110587
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author Wang, Dahai
Tanaka-Yano, Mayuri
Meader, Eleanor
Kinney, Melissa A.
Morris, Vivian
Lummertz da Rocha, Edroaldo
Liu, Nan
Liu, Tianxin
Zhu, Qian
Orkin, Stuart H.
North, Trista E.
Daley, George Q.
Rowe, R. Grant
author_facet Wang, Dahai
Tanaka-Yano, Mayuri
Meader, Eleanor
Kinney, Melissa A.
Morris, Vivian
Lummertz da Rocha, Edroaldo
Liu, Nan
Liu, Tianxin
Zhu, Qian
Orkin, Stuart H.
North, Trista E.
Daley, George Q.
Rowe, R. Grant
author_sort Wang, Dahai
collection PubMed
description Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7’s control of hematopoietic maturation. We find that juvenile Cbx2(−/−) hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders.
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spelling pubmed-90292602022-04-22 Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis Wang, Dahai Tanaka-Yano, Mayuri Meader, Eleanor Kinney, Melissa A. Morris, Vivian Lummertz da Rocha, Edroaldo Liu, Nan Liu, Tianxin Zhu, Qian Orkin, Stuart H. North, Trista E. Daley, George Q. Rowe, R. Grant Cell Rep Article Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7’s control of hematopoietic maturation. We find that juvenile Cbx2(−/−) hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders. 2022-04-05 /pmc/articles/PMC9029260/ /pubmed/35385744 http://dx.doi.org/10.1016/j.celrep.2022.110587 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Wang, Dahai
Tanaka-Yano, Mayuri
Meader, Eleanor
Kinney, Melissa A.
Morris, Vivian
Lummertz da Rocha, Edroaldo
Liu, Nan
Liu, Tianxin
Zhu, Qian
Orkin, Stuart H.
North, Trista E.
Daley, George Q.
Rowe, R. Grant
Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title_full Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title_fullStr Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title_full_unstemmed Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title_short Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis
title_sort developmental maturation of the hematopoietic system controlled by a lin28b-let-7-cbx2 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029260/
https://www.ncbi.nlm.nih.gov/pubmed/35385744
http://dx.doi.org/10.1016/j.celrep.2022.110587
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