Hanae Lahlou

Hanae Lahlou
Aix-Marseille Université | AMU · Laboratoire Cognitive Neuroscience

About

38
Publications
1,497
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78
Citations

Publications

Publications (38)
Article
Full-text available
We analyzed transcriptomic data from otic sensory cells differentiated from human induced pluripotent stem cells (hiPSCs) by a previously described method to gain new insights into the early human otic neurosensory lineage. We identified genes and biological networks not previously described to occur in the human otic sensory developmental cell lin...
Article
Full-text available
Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this p...
Cover Page
On the Cover: The image is a representative histological transverse section of ototoxic drug-deafened guinea pig cochlea 2 weeks post-transplantation of human otic progenitor cells (hOPCs) derived from induced pluripotent stem cells. The section visualizes hOPCs (red) that migrated along the basal-to-apical longitudinal axis of the grafted cochlea...
Method
Full-text available
In Vitro Induction and In Vivo Engraftment of Otic Progenitor Cells (hOPCs) Derived from Human Pluripotent Stem Cells into Ototoxic Drug Deafened Guinea pig Cochlea.
Cover Page
Full-text available
On the Cover: The image is a representative histological transverse section of ototoxic drug-deafened guinea pig cochlea 2 weeks post-transplantation of human otic progenitor cells (hOPCs) derived from induced pluripotent stem cells. The section visualizes hOPCs (red) that migrated along the basal-to-apical longitudinal axis of the grafted cochlea...
Article
Full-text available
Most cases of sensorineural deafness are caused by degeneration of hair cells. Although stem/progenitor cell therapy is becoming a promising treatment strategy in a variety of organ systems, cell engraftment in the adult mammalian cochlea has not yet been demonstrated. In this study, we generated human otic progenitor cells (hOPCs) from induced plu...
Article
Full-text available
Age-related neurosensory deficit of the inner ear is mostly due to a loss of hair cells (HCs). Development of stem cell-based therapy requires a better understanding of factors and signals that drive stem cells into otic sensory progenitor cells (OSPCs) to replace lost HCs. Human induced pluripotent stem cells (hiPSCs) theoretically represent an un...
Data
Generation of otic/placodal progenitor cells at day 6 of differentiation. Early differentiating SOX2 and PAX2 immuno-positive cells from hiPSCs in FGF3 + FGF10 (A) and FSBD (B) cultures. In FSBD-treated cultures, we observed a large population of SOX2 (shown in green) and PAX2 (shown in white) immuno-positive when compared to FGF3/10-treated cultur...
Data
Functional network analysis related WNT gene markers upregulated during the time course of in vitro otic induction. (A) The most significant IPA network assembled around WNT in day 13 cultures showing the network of WNT and their close interactions with SOX9 and Hedgehog genes. Genes upregulated included in the day 13 signature are in pink and thos...
Data
Functional network analysis related to day 6 and day 13 up-regulated genes. (A) Characterization of Sonic Hedgehog signaling pathway during in vitro differentiation of hiPSCs to hOPCs. Genes shown in pink are up-regulated in day 6 and day 13 and in green are downregulated genes. (B) Figure shows read numbers of Sonic Hedgehog pathway related genes...
Data
Ingenuity pathway analysis showing WNT and TGF-β pathway components up-regulated in day 13 signature. The color intensity indicates their degree of upregulation. Downregulated genes are shown in green and upregulated genes are shown in pink. Uncolored genes were identified as not differentially expressed in our analysis. The deregulated genes were...
Data
Significant network and genes assembled around NOTCH pathway. (A) Gene interaction networks were constructed using the IPA software. Nodes shaded in pink represent genes that are upregulated in day 6 and day 13, and green nodes are genes that are downregulated in day 6 and day 13 cultures. These networks assembled by up- and down-regulated genes in...
Data
List of gene-specific primers used for RT-qPCR for gene expression.
Data
List of primary and secondary antibodies used for immunohistochemistry.
Article
Age-related neurosensory deficit of the inner ear is mostly due to a loss of hair cells (HCs). Development of stem cell-based therapy requires a better understanding of factors and signals that drive stem cells into otic sensory progenitor cells (OSPCs) to replace lost HCs. Human induced pluripotent stem cells (hiPSCs) theoretically represent an un...
Article
Full-text available
The inner ear represents a promising system to develop cell-based therapies from human induced pluripotent stem cells (hiPSCs). In the developing ear, Notch signaling plays multiple roles in otic region specification and for cell fate determination. Optimizing hiPSC induction for the generation of appropriate numbers of otic progenitors and derivat...
Data
Analysis of pluripotency and otic gene markers by RT-QPCR during the time course of hiPSC differentiation. (A) A progressive downregulation in the relative gene expression of a subset of pluripotency factors during differentiation processes following exposition to FGF3/10 and RA/EGF at day 13 (B) and day 20 (C) cultures respectively. (D) Expression...
Data
List of antibodies used in immunocytochemical marker expression studies. (DOCX)
Data
Characterization of pluripotency markers of cultured hiPSCs. Immunostaining of undifferentiated hiPSCs with antibodies specific for pluripotency markers: NANOG, SSEA4, OCT4, SOX2, and AP activity. (A-C) The pluripotency marker molecules were expressed in virtually all the propagated cells. The immunostaining also revealed the lack of the early diff...
Data
A gene expression panel of six known supporting cell markers during the time course of hiPSC differentiation. RT-qPCR for changes of supporting cell markers at day 13 and day 20 of differentiation in comparison to undifferentiated cells at day 0, normalized to GAPDH gene. Expression analyses show increase in transcripts of S100A1, LGR5, JAG1, HEY1...
Data
Otic sensory cell cultures previously exposed to DBZ were maintained for one additional week (day-27) in DFNB culture medium. These differentiated cultures displayed MYO7A + cells (shown in red) intermixed with a large population of SOX2 expressing cells (shown in green) (A-A’). Scale bar = 50 μm. (TIF)
Data
Generation of otic/placodal cells from hiPSCs cultures at day 13 of in vitro differentiation. Representative double immunostainings for PAX2 and SOX2 (A-A”) and for PAX2 and DLX5 (B-B”) in FGF3/10 cell cultures. A population of PAX2 and SOX2 double immuno+ cells (dotted circle) are observed in these differentiated cultures. In some areas within the...
Data
Quantification of otic/placodal labeled cell expression of differentiated cells in FGF3/10 cultures at day 6 and day 13 in vitro. The individual bars visualize the fraction of positive immunolabelled cells to the total number of Hoechst labeled-cells examined in eleven randomly selected distinct fields from five coverslips (n = 1). (TIF)
Data
List of gene-specific primers used for RT-qPCR for gene expression studies. (DOCX)
Conference Paper
In mammals including human, auditory hair cells (HCs) are produced only during embryonic development and do not regenerate, therefore if these cells are lost during postnatal and adult life, the result is profound sensori-neural deafness. Noteworthy, the inner ear represents another system of interest for drug discovery and cell therapy. Stem cell-...
Conference Paper
In mammals including human, auditory hair cells (HCs) are produced only during embryonic development and do not regenerate, therefore if these cells are lost during postnatal and adult life, the result is profound sensori-neural deafness. Noteworthy, the inner ear represents another system of interest for drug discovery and cell therapy. Stem cell-...
Article
Full-text available
Stem cell-based therapies critically rely on selective cell migration toward pathological or injured areas. We previously demonstrated that human olfactory ectomesenchymal stem cells (OE-MSCs), derived from an adult olfactory lamina propria, migrate specifically toward an injured mouse hippocampus after transplantation in the cerebrospinal fluid an...
Conference Paper
Fluorescent activated cell sorting (FACS) combined with high efflux capacity for Hoechst dye for enrichment of Hair Cell Progenitors from the Postnatal Mouse Cochlea
Data
The information of supplementary materials are as follows: Supplementary table 1. List of proteins secreted by OE-MSCs. Supplementary table 2: Mouse and human target and control probes used in RT-qPCR.
Conference Paper
Human induced pluripotent stem cells (hiPSCs) technology holds great expectations for drug discovery and cell therapy applications. Recent progresses have been made in applying hiPSC technology to a variety of organ systems such as the retina, as well as the peripheral and central nervous systems. Noteworthy, the inner ear represents another system...

Questions

Questions (2)
Question
notch signaling inhibitor
Question
role of gamma secretase in Notch signaling pathway 

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Projects

Project (1)
Project
- Controlling proliferation and differentiation in human stem cells intended for therapeutic use. - Drug screnning for inner ear hair cells protection and regeneration - In vitro and in vivo investigations of stem cells and drug based therapies in hearing loss models