Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme int...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/6/1472 |
| _version_ | 1797565149143367680 |
|---|---|
| author | Anna L. Höving Kazuko E. Schmidt Madlen Merten Jassin Hamidi Ann-Katrin Rott Isabel Faust Johannes F. W. Greiner Jan Gummert Barbara Kaltschmidt Christian Kaltschmidt Cornelius Knabbe |
| author_facet | Anna L. Höving Kazuko E. Schmidt Madlen Merten Jassin Hamidi Ann-Katrin Rott Isabel Faust Johannes F. W. Greiner Jan Gummert Barbara Kaltschmidt Christian Kaltschmidt Cornelius Knabbe |
| author_sort | Anna L. Höving |
| collection | DOAJ |
| description | During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells. |
| first_indexed | 2024-03-10T19:07:49Z |
| format | Article |
| id | doaj.art-245b264f33af44c19efd1b718d68202f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:07:49Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-245b264f33af44c19efd1b718d68202f2023-11-20T04:00:49ZengMDPI AGCells2073-44092020-06-0196147210.3390/cells9061472Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem CellsAnna L. Höving0Kazuko E. Schmidt1Madlen Merten2Jassin Hamidi3Ann-Katrin Rott4Isabel Faust5Johannes F. W. Greiner6Jan Gummert7Barbara Kaltschmidt8Christian Kaltschmidt9Cornelius Knabbe10Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyAG Molecular Neurobiology, University of Bielefeld, 33615 Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyInstitute for Laboratory- and Transfusion Medicine, Heart and Diabetes Centre NRW, Ruhr University Bochum, 32545 Bad Oeynhausen, GermanyDepartment of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyDepartment of Thoracic and Cardiovascular surgery, Heart and Diabetes Centre NRW, Ruhr-University Bochum, 32545 Bad Oeynhausen, GermanyAG Molecular Neurobiology, University of Bielefeld, 33615 Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, 33615 Bielefeld, GermanyInstitute for Laboratory- and Transfusion Medicine, Heart and Diabetes Centre NRW, Ruhr University Bochum, 32545 Bad Oeynhausen, GermanyDuring aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells.https://www.mdpi.com/2073-4409/9/6/1472blood serumheart stem cellsp38-MAPKRNAseq |
| spellingShingle | Anna L. Höving Kazuko E. Schmidt Madlen Merten Jassin Hamidi Ann-Katrin Rott Isabel Faust Johannes F. W. Greiner Jan Gummert Barbara Kaltschmidt Christian Kaltschmidt Cornelius Knabbe Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells Cells blood serum heart stem cells p38-MAPK RNAseq |
| title | Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells |
| title_full | Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells |
| title_fullStr | Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells |
| title_full_unstemmed | Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells |
| title_short | Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells |
| title_sort | blood serum stimulates p38 mediated proliferation and changes in global gene expression of adult human cardiac stem cells |
| topic | blood serum heart stem cells p38-MAPK RNAseq |
| url | https://www.mdpi.com/2073-4409/9/6/1472 |
| work_keys_str_mv | AT annalhoving bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT kazukoeschmidt bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT madlenmerten bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT jassinhamidi bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT annkatrinrott bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT isabelfaust bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT johannesfwgreiner bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT jangummert bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT barbarakaltschmidt bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT christiankaltschmidt bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells AT corneliusknabbe bloodserumstimulatesp38mediatedproliferationandchangesinglobalgeneexpressionofadulthumancardiacstemcells |