Transcriptomic signatures of individual cell types in cerebral cavernous malformation
Abstract Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Ddgp6MUP9uoWsxMj-KUiCyVideo Abstract.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Cell communication and signaling - 22(2024), 1 vom: 09. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Ying [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
Cell–cell interaction |
|---|
| Anmerkungen: |
© The Author(s) 2024 |
|---|
| doi: |
10.1186/s12964-023-01301-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR054326567 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR054326567 | ||
| 003 | DE-627 | ||
| 005 | 20240110064648.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240110s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12964-023-01301-2 |2 doi | |
| 035 | |a (DE-627)SPR054326567 | ||
| 035 | |a (SPR)s12964-023-01301-2-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Ying |e verfasserin |0 (orcid)0000-0002-4107-5442 |4 aut | |
| 245 | 1 | 0 | |a Transcriptomic signatures of individual cell types in cerebral cavernous malformation |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s) 2024 | ||
| 520 | |a Abstract Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Ddgp6MUP9uoWsxMj-KUiCyVideo Abstract | ||
| 650 | 4 | |a Cerebral cavernous malformation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a VEGFA/VEGFR2 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Transcriptome |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cell–cell interaction |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Girard, Romuald |4 aut | |
| 700 | 1 | |a Srinath, Abhinav |4 aut | |
| 700 | 1 | |a Cruz, Diana Vera |4 aut | |
| 700 | 1 | |a Ciszewski, Cezary |4 aut | |
| 700 | 1 | |a Chen, Chang |4 aut | |
| 700 | 1 | |a Lightle, Rhonda |4 aut | |
| 700 | 1 | |a Romanos, Sharbel |4 aut | |
| 700 | 1 | |a Sone, Je Yeong |4 aut | |
| 700 | 1 | |a Moore, Thomas |4 aut | |
| 700 | 1 | |a DeBiasse, Dorothy |4 aut | |
| 700 | 1 | |a Stadnik, Agnieszka |4 aut | |
| 700 | 1 | |a Lee, Justine J. |4 aut | |
| 700 | 1 | |a Shenkar, Robert |0 (orcid)0000-0002-1300-6845 |4 aut | |
| 700 | 1 | |a Koskimäki, Janne |4 aut | |
| 700 | 1 | |a Lopez-Ramirez, Miguel A. |4 aut | |
| 700 | 1 | |a Marchuk, Douglas A. |4 aut | |
| 700 | 1 | |a Ginsberg, Mark H. |4 aut | |
| 700 | 1 | |a Kahn, Mark L. |4 aut | |
| 700 | 1 | |a Shi, Changbin |4 aut | |
| 700 | 1 | |a Awad, Issam A. |0 (orcid)0000-0003-1510-602X |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell communication and signaling |d London : Biomed Central, 2003 |g 22(2024), 1 vom: 09. Jan. |w (DE-627)SPR028900014 |w (DE-600)2126315-2 |x 1478-811X |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:1 |g day:09 |g month:01 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/s12964-023-01301-2 |z kostenfrei |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 1 |b 09 |c 01 | ||