Back

Path of differentiation defines human macrophage identity

Frenis, K.; Badalamenti, B.; Mamigonian, O.; Weng, C.; Wang, D.; Fierstein, S.; Cote, P.; Khong, H.; Li, H.; Lummertz da Rocha, E.; Sankaran, V.; Rowe, R. G.

2025-01-24 molecular biology
10.1101/2025.01.24.634694 bioRxiv
Show abstract

Macrophages play central roles in immunity, wound healing, and homeostasis - a functional diversity that is underpinned by varying developmental origins. The impact of ontogeny on properties of human macrophages is inadequately understood. We demonstrate that definitive human fetal liver (HFL) hematopoietic stem cells (HSCs) possess two divergent paths of macrophage specification that lead to distinct identities. The monocyte-dependent pathway exists in both prenatal and postnatal hematopoiesis and generates macrophages with adult-like responses properties. We now uncover a fetal-specific pathway of expedited differentiation that generates tissue resident-like macrophages (TRMs) that retain HSC-like self-renewal programs governed by the aryl hydrocarbon receptor (AHR). We show that AHR antagonism promotes TRM expansion and mitigates inflammation in models of atopic dermatitis (AD). Overall, we directly connect path of differentiation with functional properties of macrophages and identify an approach to promote selective expansion of TRMs with direct relevance to inflammation and diseases of macrophage dysfunction.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 9%
18.3%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 1.0%
12.5%
Similar papers in this journal
3
Cell Stem Cell
○ 62 papers in training set
Top 0.1%
10.5%
Similar papers in this journal
4
eLife
● 5828 papers in training set
Top 20%
6.2%
Similar papers in this journal
5
HemaSphere
○ 16 papers in training set
Top 0.1%
3.4%
Similar papers in this journal
50% of probability mass above
6
Blood
● 74 papers in training set
Top 0.6%
3.2%
7
Cell
○ 431 papers in training set
Top 3%
3.2%
8
Stem Cell Reports
○ 130 papers in training set
Top 0.8%
3.1%
9
Science Advances
● 1243 papers in training set
Top 12%
3.1%
10
Molecular Cell
○ 350 papers in training set
Top 2%
2.6%
11
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 26%
1.9%
12
Cell Genomics
○ 172 papers in training set
Top 2%
1.9%
13
iScience
○ 1154 papers in training set
Top 16%
1.9%
14
The EMBO Journal
○ 309 papers in training set
Top 3%
1.9%
15
Communications Biology
○ 993 papers in training set
Top 18%
1.4%
16
Nature Cell Biology
○ 118 papers in training set
Top 2%
1.1%
17
Journal of Clinical Investigation
● 179 papers in training set
Top 4%
1.1%
18
Cell Metabolism
○ 57 papers in training set
Top 1%
1.1%
19
Science
● 477 papers in training set
Top 7%
1.1%
20
Nature
○ 645 papers in training set
Top 10%
1.0%
21
Developmental Cell
○ 196 papers in training set
Top 4%
0.8%
22
Scientific Reports
○ 3612 papers in training set
Top 73%
0.8%
23
EMBO Reports
○ 263 papers in training set
Top 8%
0.6%
24
Cell Reports Medicine
○ 153 papers in training set
Top 6%
0.6%
25
Mucosal Immunology
○ 47 papers in training set
Top 1%
0.6%
26
Cell Death & Differentiation
○ 48 papers in training set
Top 2%
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.