#PartialReprogramming
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The Phase 1 trial of ER-100, which activates Yamanaka factors in the eye, did not cause serious adverse events in three participants. Early visual field signals were observed in two of the three patients with open-angle glaucoma.

#PartialReprogramming #ER100 #Glaucoma
Two of three glaucoma patients showed early visual-field signals
Source: Longevity.Technology
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October 9, 2026 at 6:00 AM
alicefrolov.bsky.social
Sharing a visualization from a methodological exercise on partial reprogramming kinetics that may be of interest to colleagues working on in vivo epigenetic rejuvenation paradigms.

#PartialReprogramming #YamanakaFactors #EpigeneticRejuvenation #AgingBiology #InVivoReprogramming
Sharing a visualization from a methodological exercise on partial reprogramming kinetics that may be of interest to colleagues working on in vivo epigenetic rejuvenation paradigms. **Figure:** Transient OSKM Induction Kinetics in Doxycycline-Pulsed Reprogrammable Mice **Subtitle:** Relative transcript abundance of each Yamanaka factor over a 7-day induction–withdrawal cycle in liver The multiline plot tracks normalized mRNA levels of Oct4 (Pou5f1), Sox2, Klf4, and c-Myc across a canonical short-cycle doxycycline regimen in a tetO-OSKM; Rosa26-M2rtTA background, with hepatic tissue as the sampled compartment. The temporal window spans a 48-hour dox administration phase followed by a 5-day washout, capturing induction onset, transgene saturation, and post-withdrawal decay. Key features rendered in the visualization: - Rapid transactivation of all four cassettes within 12–24 h post-dox, with c-Myc and Klf4 displaying the steepest initial slopes, consistent with their reported transcriptional responsiveness and shorter transcript half-lives. - Asynchronous peak amplitudes: Oct4 and Sox2 reach maxima at ~36–48 h, while c-Myc plateaus earlier, reflecting differential polycistronic cassette dynamics and endogenous locus contributions. - Post-withdrawal decay follows factor-specific kinetics; c-Myc transcripts return to near-baseline within 48 h of dox removal, whereas Oct4 exhibits a more protracted decline — relevant when designing cyclic regimens intended to avoid teratoma risk while sustaining epigenetic remodeling. - Absence of overt lineage-inappropriate marker induction within the plotted window, consistent with the sub-dedifferentiation threshold characteristic of partial reprogramming protocols (cf. Ocampo et al., 2016; Browder et al., 2022; Chondronasiou et al., 2022).
July 10, 2026 at 5:03 PM
alicefrolov.bsky.social
Sharing a visualization developed for didactic and exploratory purposes, addressing the temporal dynamics of OSKM-mediated reprogramming in somatic cells.

#CellularReprogramming #YamanakaFactors #iPSC #Pluripotency #Epigenetics #Senescence #PartialReprogramming #SystemsBiology
Sharing a visualization developed for didactic and exploratory purposes, addressing the temporal dynamics of OSKM-mediated reprogramming in somatic cells. Figure: "Partial reprogramming progressively erodes somatic identity" Subtitle: "Transcriptional trajectories of fibroblast, pluripotency, and senescence markers during OSKM induction" The multiline plot tracks normalized expression trajectories of three marker classes across a continuous induction window (0–20 days of doxycycline-driven OSKM expression): 1. Somatic/fibroblast identity markers (Col1a1, Thy1, S100a4, Fsp1) exhibit monotonic downregulation, with inflection between days 4–8 consistent with the loss of mesenchymal transcriptional programs that precedes MET. 2. Pluripotency-associated loci (Nanog, Esrrb, endogenous Oct4, Sox2) display the canonical biphasic trajectory: a latent phase (days 0–6), followed by stochastic activation and, in a subset of trajectories, deterministic stabilization beyond day 12, recapitulating the late hierarchical activation described by Polo, Buganim, and Hochedlinger and colleagues. 3. Senescence/stress markers (Cdkn2a/p16, Cdkn1a/p21, IL6) show a transient peak between days 3–9, mirroring the OSKM-induced senescence barrier and its paracrine reinforcement. The figure is intended to make explicit the inverse coupling between somatic dedifferentiation kinetics and the senescence-associated barrier, and to delineate the partial reprogramming window (approximately days 4–8) in which somatic identity is substantially eroded before robust pluripotency network activation — the regime exploited in transient OSKM rejuvenation paradigms (Ocampo et al., 2016; Browder et al., 2022). The data plotted are simulated. Trajectories were parameterized to reflect qualitative trends consolidated in the reprogramming literature (MEF→iPSC transitions, secondary reprogramming systems, single-cell lineage tracing studies) and do not correspond to any specific experimental dataset.
June 28, 2026 at 5:03 PM
alicefrolov.bsky.social
Transient OSKM induction dynamics in aged fibroblasts: relative transcript abundance over a 6-day doxycycline pulse-chase.

#PartialReprogramming #YamanakaFactors #CellularRejuvenation #EpigeneticReprogramming #OSKM #AgingBiology #TranscriptionalDynamics #SystemsBiology
Transient OSKM induction dynamics in aged fibroblasts: relative transcript abundance over a 6-day doxycycline pulse-chase Sharing a visualization developed in the context of our ongoing methodological work on partial reprogramming protocols. The figure depicts the temporal kinetics of the four Yamanaka factors (Oct4, Sox2, Klf4, c-Myc) at the transcript level across a 6-day window encompassing a doxycycline-inducible pulse followed by withdrawal, in a Tet-On system expressed in late-passage murine dermal fibroblasts. The multiline plot tracks normalized mRNA abundance (relative to Gapdh, log2 fold change over uninduced baseline) sampled at 12-hour intervals. Several features are worth highlighting for discussion: - Asynchronous induction onset: c-Myc and Klf4 transcripts rise with shorter latency than Oct4 and Sox2, consistent with reported differences in transactivator binding kinetics and endogenous chromatin accessibility at the respective loci. - Plateau asymmetry: Klf4 reaches the highest steady-state amplitude during the induction phase, while Sox2 exhibits the most attenuated response, in line with stoichiometric imbalances repeatedly documented in polycistronic OSKM cassettes. - Decay kinetics post-dox withdrawal: exogenous transcript clearance follows approximately first-order decay, with c-Myc displaying the shortest apparent half-life and Oct4 the longest residual signal, reflecting both mRNA stability and 3'UTR-dependent turnover. - The chosen 48-hour induction window is intended to remain below the somatic identity loss threshold reported by Ocampo et al. (2016) and subsequent studies, while still being sufficient to engage early epigenetic remodeling. Important caveat: the data plotted here are simulated and serve an illustrative purpose. #PartialReprogramming #YamanakaFactors #CellularRejuvenation #EpigeneticReprogramming #OSKM #AgingBiology #TranscriptionalDynamics #SystemsBiology
June 26, 2026 at 5:01 PM
alicefrolov.bsky.social
Epigenetic age reversal kinetics under partial versus complete Yamanaka factor-mediated reprogramming

Transient induction of OCT4, SOX2, and KLF4 (OSK) or the complete OSKM cassette.

#EpigeneticReprogramming #YamanakaFactors #PartialReprogramming #EpigeneticClock #OSK #Rejuvenation #AgingBiology
Epigenetic age reversal kinetics under partial versus complete Yamanaka factor-mediated reprogramming Transient induction of OCT4, SOX2, and KLF4 (OSK) — or the complete OSKM cassette — drives progressive erasure of age-associated epigenetic marks, quantifiable via Horvath-family methylation clocks as negative delta biological age. Partial reprogramming protocols, defined by abbreviated factor expression prior to loss of somatic identity, achieve significant epigenetic rejuvenation while preserving cell-type-specific transcriptional programs — a critical distinction from complete reprogramming, which traverses a pluripotent intermediate with associated risks of teratoma formation and epigenetic dysregulation. The dose-response relationship between reprogramming cycle number and clock-measured age reversal suggests saturable resetting of methylation at clock CpGs, with diminishing returns beyond a tissue-specific threshold. Mechanistically, OSK-mediated rejuvenation is proposed to operate through TET-dependent active demethylation at age-hypermethylated loci and restoration of H3K27me3 patterning at Polycomb targets — implicating chromatin remodeling upstream of transcriptional identity restoration. These findings position partial reprogramming as the most mechanistically proximate intervention to date for reversing the epigenetic component of cellular aging.
May 29, 2026 at 5:00 PM