Back

Lung endothelial niche signaling governs self-renewal and fate transitions of human alveolar stem cells

Kim, B.-J.; Hwang, D.; Park, J.; Jang, S. J.; Kim, J.; Camillo, C.; Floris, E.; Choi, A.; Ryu, S.; D'Ovidio, F.; Ryeom, S.

2026-03-09 cell biology
10.64898/2026.03.07.710316 bioRxiv
Show abstract

Chronic lung diseases such as pulmonary fibrosis are characterized by the irreversible loss of alveolar type 1 (AT1) cells, yet the mechanisms governing human alveolar stem cell self-renewal and differentiation remain poorly defined. Here, we identify a lung endothelial niche that sustains the self-renewal of human alveolar type 2 (AT2) stem cells through MAPK signaling, enabling robust long-term expansion while preserving stem cell fate. Although YAP activation initiates AT1 transcriptional programs, it is insufficient to complete lineage maturation. We show that MAPK inhibition together with LATS inhibition promotes nuclear translocation of YAP, enhancing AT1 differentiation. Expanded human AT2 stem cells engraft in fibrotic lungs and contribute to alveolar regeneration while undergoing directed differentiation within diseased human lung tissue. Together, our findings define a niche-controlled signaling mechanism governing human alveolar stem cell fate and advance our understanding of alveolar regeneration.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
Nature Communications
4913 papers in training set
Top 7%
17.8%
2
Cell Stem Cell
57 papers in training set
Top 0.1%
16.8%
3
Developmental Cell
168 papers in training set
Top 1%
11.8%
4
Nature Cell Biology
99 papers in training set
Top 0.4%
8.0%
50% of probability mass above
5
Nature
575 papers in training set
Top 5%
6.0%
6
Cell Reports
1338 papers in training set
Top 18%
2.9%
7
Journal of Experimental Medicine
106 papers in training set
Top 2%
2.0%
8
eLife
5422 papers in training set
Top 39%
1.8%
9
Proceedings of the National Academy of Sciences
2130 papers in training set
Top 30%
1.8%
10
Molecular Cell
308 papers in training set
Top 6%
1.8%
11
Science Advances
1098 papers in training set
Top 19%
1.6%
12
Nature Immunology
71 papers in training set
Top 1%
1.6%
13
Immunity
58 papers in training set
Top 3%
1.3%
14
JCI Insight
241 papers in training set
Top 5%
1.3%
15
Science
429 papers in training set
Top 17%
1.2%
16
Advanced Science
249 papers in training set
Top 15%
1.2%
17
Nature Medicine
117 papers in training set
Top 4%
0.9%
18
Cell Research
49 papers in training set
Top 2%
0.9%
19
Cancer Discovery
61 papers in training set
Top 2%
0.9%
20
Circulation
66 papers in training set
Top 2%
0.9%
21
The EMBO Journal
267 papers in training set
Top 4%
0.9%
22
American Journal of Respiratory and Critical Care Medicine
39 papers in training set
Top 0.9%
0.8%
23
Nature Genetics
240 papers in training set
Top 7%
0.8%
24
Nature Metabolism
56 papers in training set
Top 3%
0.7%
25
Cell Metabolism
49 papers in training set
Top 3%
0.7%
26
Science Translational Medicine
111 papers in training set
Top 7%
0.7%
27
Journal of Clinical Investigation
164 papers in training set
Top 7%
0.7%
28
Cell
370 papers in training set
Top 18%
0.7%
29
Nucleic Acids Research
1128 papers in training set
Top 19%
0.7%
30
Nature Aging
51 papers in training set
Top 2%
0.6%