# Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges

**Authors:** Fulvio Bonsignore, Sara Pozzi, Erika Aloi, Davide Mazza, Samuel Zambrano

PMC · DOI: 10.3389/fcell.2025.1656051 · Frontiers in Cell and Developmental Biology · 2025-10-23

## TL;DR

This paper reviews how dynamic signaling in individual cells influences cell fate decisions and highlights the evidence and challenges in this area.

## Contribution

The paper provides a conceptual framework and unifying view of methodologies linking signaling dynamics to cell fate decisions.

## Key findings

- Signaling dynamics play a functional role in determining cell fate across various biological contexts.
- There is a need for better mechanistic understanding of how temporal signaling affects cellular responses.

## Abstract

Our ever-growing capacity to observe dynamic processes at the single-cell level has highlighted how cells use complex signaling dynamics to provide adequate responses to intra- and extracellular cues. Specifically, there is increasing evidence that signaling dynamics can be functional in determining cell fate decisions. In this work, we provide an overview of the growing body of evidence supporting this idea across diverse biological contexts—including immune responses, reactions to DNA damage and growth factors, and embryonic development. In doing so, we aim to provide a precise conceptualization of what is meant when we say that signaling dynamics can determine cell fate, a unifying view of the methodologies used to sustain this claim and to identify some of the existing gaps in our mechanistic understanding of this process. We believe that the body of work hereby described strongly supports the importance of considering the temporal dimension of signaling when seeking to understand how cellular responses are regulated.

## Full-text entities

- **Genes:** Ephb1 (Eph receptor B1) [NCBI Gene 24338] {aka Ephb2, Erk, elk}, Nanog (Nanog homeobox) [NCBI Gene 71950] {aka 2410002E02Rik, ENK, Stm1, ecat4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Epidermal Growth Factor [NCBI Gene 108348113], Mdm2 (MDM2 proto-oncogene) [NCBI Gene 17246] {aka 1700007J15Rik, Mdm-2}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, Atr (ataxia telangiectasia and Rad3 related) [NCBI Gene 245000], Tnfaip3 (tumor necrosis factor, alpha-induced protein 3) [NCBI Gene 21929] {aka A20, Tnfip3}, Jag1 (jagged 1) [NCBI Gene 16449] {aka ABE2, Gena228, Gsfabe2, Htu, Ozz, Ser-1}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Iap1-3 (intracisternal A particle, Eya1 linked) [NCBI Gene 15601] {aka IAP}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Xiap (X-linked inhibitor of apoptosis) [NCBI Gene 11798] {aka 1110015C02Rik, Aipa, Api3, Birc4, IAP3, ILP-1}, Neurog2 (neurogenin 2) [NCBI Gene 11924] {aka Atoh4, Math4A, bHLHa8, ngn-2, ngn2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, Dll4 (delta like canonical Notch ligand 4) [NCBI Gene 54485] {aka Delta4}, Relb (Relb proto-oncogene, NFKB subunit) [NCBI Gene 19698] {aka shep}, Hes7 (hes family bHLH transcription factor 7) [NCBI Gene 84653] {aka bHLHb37}, Neurod4 (neurogenic differentiation 4) [NCBI Gene 11923] {aka ATH-3, Atoh3, MATH-3, Math3, bHLHa4}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, Ascl1 (achaete-scute family bHLH transcription factor 1) [NCBI Gene 17172] {aka ASH1, Mash1, bHLHa46}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, Notch1 (notch 1) [NCBI Gene 18128] {aka 9930111A19Rik, Mis6, N1, Tan1, lin-12}, Cd83 (CD83 antigen) [NCBI Gene 12522], Itpr3 (inositol 1,4,5-triphosphate receptor 3) [NCBI Gene 16440] {aka IP3R 3, IP3R-3, Ip3r3, Itpr-3, tf}, Hes1 (hes family bHLH transcription factor 1) [NCBI Gene 15205] {aka Hry, bHLHb39}, Egf (epidermal growth factor) [NCBI Gene 25313], Hes5 (hes family bHLH transcription factor 5) [NCBI Gene 15208] {aka bHLHb38}, Dll1 (delta like canonical Notch ligand 1) [NCBI Gene 13388] {aka Delta1}, Atcay (ataxia, cerebellar, Cayman type) [NCBI Gene 16467] {aka 3322401A10Rik, BNIP-H, CLAC, hes, ji}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, Neurog3 (neurogenin 3) [NCBI Gene 11925] {aka Atoh5, Math4B, bHLHa7, ngn3}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, Ppm1d (protein phosphatase 1D magnesium-dependent, delta isoform) [NCBI Gene 53892] {aka Wip1}, Nfkb2 (nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100) [NCBI Gene 18034] {aka NF-kappaB2, lyt, p49, p49/p100, p50B, p52}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, Rel (Rel proto-oncogene, NFKB subunit) [NCBI Gene 19696] {aka c-Rel}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, rl (rolled) [NCBI Gene 3354888] {aka 12559, BcDNA:RE08694, CG12559, CG18732, CT34260, CT39192}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}
- **Diseases:** inflammation (MESH:D007249), DM (MESH:D009223), cancer (MESH:D009369)
- **Chemicals:** Ca2+ (-), cisplatin (MESH:D002945), Etoposide (MESH:D005047), Nutlin-3a (MESH:C482205)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Xenopus laevis (African clawed frog, species) [taxon 8355], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), MCF10 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), L929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12588912/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12588912/full.md

## References

187 references — full list in the complete paper: https://tomesphere.com/paper/PMC12588912/full.md

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Source: https://tomesphere.com/paper/PMC12588912