Alveolar Regeneration 2D: Krt8+ Transitional Cell-State Map

Injury & Regeneration

Injury severity 50%

Resolution rate (WNT / EGFR) 0.60 /day

ATII proliferation rate 0.50 /day

Cell-State Population

ATII (stem) 30% Krt8⁺ transitional 0% ATI (mature) 70% Dead / empty 0%

Fibrotic signalling burden

Elapsed time

0.0 d

Cells regenerated

How it works

This is the 2D top-down companion to the 3D alveolar-dome simulator: the same 420 individually tracked cells, each running an independent continuous-time Markov chain, laid out here as a flat sunflower-pattern patch of epithelium you can pan and zoom instead of orbit. Every cell transitions on its own stochastic clock with per-day rates:

P(transition in dt) = 1 - e^(-rate · dt)

Dead  --k_prolif-->  ATII    (progenitor proliferation)
ATII  --k_act------>  Krt8⁺  (damage-induced activation)
Krt8⁺ --k_res------>  ATI    (WNT + EGFR-driven resolution)

Injury severity — fraction of ATII + ATI cells instantly converted to dead/empty slots when you trigger injury, mimicking viral or toxic epithelial death.
Resolution rate (k_res) — how fast Krt8⁺ cells complete differentiation into ATI. In vivo this requires WNT activation and resolution of EGFR signalling; when it's slow, transitional cells pile up.
ATII proliferation rate (k_prolif) — how fast empty slots are repopulated by self-renewing ATII progenitors, the source of new regenerating tissue.
Fibrotic signalling burden — accumulates while cells sit in the Krt8⁺ state (it expresses TGF-β and collagen). A low resolution rate traps cells there and this burden keeps climbing — the mechanism proposed to link failed alveolar regeneration to post-viral and idiopathic pulmonary fibrosis.
Senolytic — instantly clears long-resident Krt8⁺ cells back to fresh ATII, mirroring senolytic trials aimed at removing persistent transitional/senescent cells so normal regeneration can restart.
Drag to pan, scroll/pinch to zoom — inspect any patch of the epithelium up close; the underlying per-cell clocks keep running regardless of view.

ATII stem cell Krt8⁺ transitional ATI (mature) Dead / empty

drag to pan · scroll to zoom