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Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults

Older adults have significantly worse morbidity and mortality after severe trauma than younger cohorts. The competency of the innate immune response decreases with advancing age, especially after an inflammatory insult. Subsequent poor outcomes after trauma are caused in part by dysfunctional leukoc...

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Autores principales: Darden, Dijoia B., Stortz, Julie A., Hollen, McKenzie K., Cox, Michael C., Apple, Camille G., Hawkins, Russell B., Rincon, Jaimar C., Lopez, Maria-Cecilia, Wang, Zhongkai, Navarro, Eduardo, Hagen, Jennifer E., Parvataneni, Hari K., Brusko, Maigan A., Kladde, Michael, Bacher, Rhonda, Brumback, Babette A., Brakenridge, Scott C., Baker, Henry V., Cogle, Christopher R., Mohr, Alicia M., Efron, Philip A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326804/
https://www.ncbi.nlm.nih.gov/pubmed/32670283
http://dx.doi.org/10.3389/fimmu.2020.01289
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author Darden, Dijoia B.
Stortz, Julie A.
Hollen, McKenzie K.
Cox, Michael C.
Apple, Camille G.
Hawkins, Russell B.
Rincon, Jaimar C.
Lopez, Maria-Cecilia
Wang, Zhongkai
Navarro, Eduardo
Hagen, Jennifer E.
Parvataneni, Hari K.
Brusko, Maigan A.
Kladde, Michael
Bacher, Rhonda
Brumback, Babette A.
Brakenridge, Scott C.
Baker, Henry V.
Cogle, Christopher R.
Mohr, Alicia M.
Efron, Philip A.
author_facet Darden, Dijoia B.
Stortz, Julie A.
Hollen, McKenzie K.
Cox, Michael C.
Apple, Camille G.
Hawkins, Russell B.
Rincon, Jaimar C.
Lopez, Maria-Cecilia
Wang, Zhongkai
Navarro, Eduardo
Hagen, Jennifer E.
Parvataneni, Hari K.
Brusko, Maigan A.
Kladde, Michael
Bacher, Rhonda
Brumback, Babette A.
Brakenridge, Scott C.
Baker, Henry V.
Cogle, Christopher R.
Mohr, Alicia M.
Efron, Philip A.
author_sort Darden, Dijoia B.
collection PubMed
description Older adults have significantly worse morbidity and mortality after severe trauma than younger cohorts. The competency of the innate immune response decreases with advancing age, especially after an inflammatory insult. Subsequent poor outcomes after trauma are caused in part by dysfunctional leukocytes derived from the host's hematopoietic stem and progenitor cells (HSPCs). Our objective was to analyze the bone marrow (BM) HSPC transcriptomic [mRNA and microRNA (miR)] responses to trauma in older and younger adults. BM was collected intraoperatively <9 days after initial injury from trauma patients with non-mild injury [ISS ≥ 9] or with shock (lactate ≥ 2, base deficit ≥ 5, MAP ≤ 65) who underwent operative fixation of a pelvic or long bone fracture. Samples were also analyzed based on age (<55 years and ≥55 years), ISS score and transfusion in the first 24 h, and compared to age/sex-matched controls from non-cancer elective hip replacement or purchased healthy younger adult human BM aspirates. mRNA and miR expression patterns were calculated from lineage-negative enriched HSPCs. 924 genes were differentially expressed in older trauma subjects vs. age/sex-matched controls, while 654 genes were differentially expressed in younger subjects vs. age/sex-matched control. Only 68 transcriptomic changes were shared between the two groups. Subsequent analysis revealed upregulation of transcriptomic pathways related to quantity, function, differentiation, and proliferation of HSPCs in only the younger cohort. miR expression differences were also identified, many of which were associated with cell cycle regulation. In summary, differences in the BM HSPC mRNA and miR expression were identified between older and younger adult trauma subjects. These differences in gene and miR expression were related to pathways involved in HSPC production and differentiation. These differences could potentially explain why older adult patients have a suboptimal hematopoietic response to trauma. Although immunomodulation of HSPCs may be a necessary consideration to promote host protective immunity after host injury, the age related differences further highlight that patients may require an age-defined medical approach with interventions that are specific to their transcriptomic and biologic response. Also, targeting the older adult miRs may be possible for interventions in this patient population.
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spelling pubmed-73268042020-07-14 Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults Darden, Dijoia B. Stortz, Julie A. Hollen, McKenzie K. Cox, Michael C. Apple, Camille G. Hawkins, Russell B. Rincon, Jaimar C. Lopez, Maria-Cecilia Wang, Zhongkai Navarro, Eduardo Hagen, Jennifer E. Parvataneni, Hari K. Brusko, Maigan A. Kladde, Michael Bacher, Rhonda Brumback, Babette A. Brakenridge, Scott C. Baker, Henry V. Cogle, Christopher R. Mohr, Alicia M. Efron, Philip A. Front Immunol Immunology Older adults have significantly worse morbidity and mortality after severe trauma than younger cohorts. The competency of the innate immune response decreases with advancing age, especially after an inflammatory insult. Subsequent poor outcomes after trauma are caused in part by dysfunctional leukocytes derived from the host's hematopoietic stem and progenitor cells (HSPCs). Our objective was to analyze the bone marrow (BM) HSPC transcriptomic [mRNA and microRNA (miR)] responses to trauma in older and younger adults. BM was collected intraoperatively <9 days after initial injury from trauma patients with non-mild injury [ISS ≥ 9] or with shock (lactate ≥ 2, base deficit ≥ 5, MAP ≤ 65) who underwent operative fixation of a pelvic or long bone fracture. Samples were also analyzed based on age (<55 years and ≥55 years), ISS score and transfusion in the first 24 h, and compared to age/sex-matched controls from non-cancer elective hip replacement or purchased healthy younger adult human BM aspirates. mRNA and miR expression patterns were calculated from lineage-negative enriched HSPCs. 924 genes were differentially expressed in older trauma subjects vs. age/sex-matched controls, while 654 genes were differentially expressed in younger subjects vs. age/sex-matched control. Only 68 transcriptomic changes were shared between the two groups. Subsequent analysis revealed upregulation of transcriptomic pathways related to quantity, function, differentiation, and proliferation of HSPCs in only the younger cohort. miR expression differences were also identified, many of which were associated with cell cycle regulation. In summary, differences in the BM HSPC mRNA and miR expression were identified between older and younger adult trauma subjects. These differences in gene and miR expression were related to pathways involved in HSPC production and differentiation. These differences could potentially explain why older adult patients have a suboptimal hematopoietic response to trauma. Although immunomodulation of HSPCs may be a necessary consideration to promote host protective immunity after host injury, the age related differences further highlight that patients may require an age-defined medical approach with interventions that are specific to their transcriptomic and biologic response. Also, targeting the older adult miRs may be possible for interventions in this patient population. Frontiers Media S.A. 2020-06-24 /pmc/articles/PMC7326804/ /pubmed/32670283 http://dx.doi.org/10.3389/fimmu.2020.01289 Text en Copyright © 2020 Darden, Stortz, Hollen, Cox, Apple, Hawkins, Rincon, Lopez, Wang, Navarro, Hagen, Parvataneni, Brusko, Kladde, Bacher, Brumback, Brakenridge, Baker, Cogle, Mohr and Efron. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Darden, Dijoia B.
Stortz, Julie A.
Hollen, McKenzie K.
Cox, Michael C.
Apple, Camille G.
Hawkins, Russell B.
Rincon, Jaimar C.
Lopez, Maria-Cecilia
Wang, Zhongkai
Navarro, Eduardo
Hagen, Jennifer E.
Parvataneni, Hari K.
Brusko, Maigan A.
Kladde, Michael
Bacher, Rhonda
Brumback, Babette A.
Brakenridge, Scott C.
Baker, Henry V.
Cogle, Christopher R.
Mohr, Alicia M.
Efron, Philip A.
Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title_full Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title_fullStr Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title_full_unstemmed Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title_short Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults
title_sort identification of unique mrna and mirna expression patterns in bone marrow hematopoietic stem and progenitor cells after trauma in older adults
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326804/
https://www.ncbi.nlm.nih.gov/pubmed/32670283
http://dx.doi.org/10.3389/fimmu.2020.01289
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