Back

Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14

Hirakawa, M. P.; Tjahjono, N.; Light, Y. K.; Chintalapudi, P.; Butler, K. S.; Branda, S. S.; Krishnakumar, R.

2020-10-14 molecular biology
10.1101/2020.10.14.338020 bioRxiv
Show abstract

Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic capabilities, however MSC use is confounded by cell-to-cell heterogeneity, and source-to-source phenotypic inconsistencies. We utilized a systems-based approach to compare MSCs which displayed different capacity for antibacterial activity. Although MSCs from both sources satisfied traditional MSC-defining criteria, comparative transcriptomics and quantitative membrane proteomics demonstrated two unique molecular profiles. The antibacterial MSCs respond rapidly to bacterial lipopolysaccharide (LPS) and have elevated levels of the LPS co-receptor CD14. CRISPR-mediated overexpression of endogenous CD14 in non-antibacterial MSCs resulted in faster LPS response and enhanced antimicrobial activity. Single-cell transcriptome profiling of CD14-activated MSCs revealed uniform enhancement of LPS response kinetics, and a shift in the ground state of these MSCs. Our results demonstrate that systems-level analysis can reveal critical molecular targets to optimize desirable properties in MSCs, and that overexpression of CD14 in these cells can shift their state to be more responsive to future bacterial challenge.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

1
Stem Cells
◐ 31 papers in training set
Top 0.1%
8.1%
Similar papers in this journal
2
Nature Communications
○ 5641 papers in training set
Top 20%
8.1%
Similar papers in this journal
3
eLife
● 5828 papers in training set
Top 16%
6.9%
Similar papers in this journal
4
Scientific Reports
○ 3612 papers in training set
Top 9%
6.9%
Similar papers in this journal
5
Cell Reports
○ 1498 papers in training set
Top 8%
5.0%
Similar papers in this journal
6
Communications Biology
○ 993 papers in training set
Top 2%
5.0%
7
Stem Cell Research & Therapy
○ 30 papers in training set
Top 0.1%
4.2%
8
iScience
○ 1154 papers in training set
Top 5%
3.5%
9
ACS Synthetic Biology
● 287 papers in training set
Top 1.0%
2.9%
50% of probability mass above
10
Molecular Therapy Nucleic Acids
○ 39 papers in training set
Top 0.3%
2.5%
11
Science Advances
● 1243 papers in training set
Top 17%
2.1%
12
mBio
● 833 papers in training set
Top 7%
2.0%
13
Frontiers in Immunology
○ 638 papers in training set
Top 5%
2.0%
14
Advanced Science
○ 286 papers in training set
Top 5%
1.5%
15
Biomaterials
○ 84 papers in training set
Top 1%
1.5%
16
Cells
○ 249 papers in training set
Top 4%
1.5%
17
Molecular Therapy - Nucleic Acids
○ 25 papers in training set
Top 0.4%
1.5%
18
Nucleic Acids Research
◐ 1281 papers in training set
Top 10%
1.4%
19
Molecular Medicine
○ 11 papers in training set
Top 0.1%
1.2%
20
Epigenetics
○ 50 papers in training set
Top 0.4%
1.2%
21
EMBO Reports
○ 263 papers in training set
Top 5%
1.1%
22
Frontiers in Cell and Developmental Biology
○ 233 papers in training set
Top 4%
1.1%
23
Journal of Biological Chemistry
○ 690 papers in training set
Top 9%
0.9%
24
Stem Cell Reports
○ 130 papers in training set
Top 2%
0.9%
25
PLOS ONE
● 5266 papers in training set
Top 57%
0.9%
26
Journal of The Royal Society Interface
● 235 papers in training set
Top 4%
0.9%
27
Biology Open
● 156 papers in training set
Top 3%
0.9%
28
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 40%
0.9%
29
Cell Death & Disease
147 papers in training set
Top 4%
0.6%
30
BMC Biology
○ 265 papers in training set
Top 6%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.