2022
DOI: 10.1101/2022.07.04.498717
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Directed Differentiation of Human iPSCs to Functional Ovarian Granulosa-Like Cells via Transcription Factor Overexpression

Abstract: An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and their supporting somatic cells, known as granulosa cells. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human iPSCs, a method of generating granulosa cells has been elusive. Here we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of huma… Show more

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Cited by 5 publications
(8 citation statements)
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“…Contrary to other approaches, combinatorial barcoding does not require any complex microfluidics or other specialized equipment. Over the past few years, this approach has been widely adopted to study developmental processes and disease progression at scale [13][14][15][16][17][18][19][20][21][22][23][24][25][26] .…”
Section: Introductionmentioning
confidence: 99%
“…Contrary to other approaches, combinatorial barcoding does not require any complex microfluidics or other specialized equipment. Over the past few years, this approach has been widely adopted to study developmental processes and disease progression at scale [13][14][15][16][17][18][19][20][21][22][23][24][25][26] .…”
Section: Introductionmentioning
confidence: 99%
“…For examples, overexpression of DAZL , a late germ cells marker, and BOULE , a germ cell meiotic marker, in hESCs produces DDX4- (late germ cell marker) and SYCP3- (germ meiotic marker) double positive cells, which form follicle-like structures when culture with GDF9 and BMP15 ( Jung et al, 2017 ). A recent study also used transcriptional factor library to screen critical factors for deriving granulosa cells from hiPSCs, and NR5A1 , RNUX1 or RUNX2 were identified as critical factors in granulosa cell fate decision ( Smela et al, 2022 ). The differentiated granulosa cell-like cells expressed granulosa cell markers including AMHR2 , CD82 , FOXL2 , FSHR , IGFBP7 , KRT19 , STAR , and WNT4 , and responded to exogenous FSH by producing oestrogen and progesterone ( Smela et al, 2022 ).…”
Section: Current Progress On In-vitro Differentiat...mentioning
confidence: 99%
“…A recent study also used transcriptional factor library to screen critical factors for deriving granulosa cells from hiPSCs, and NR5A1 , RNUX1 or RUNX2 were identified as critical factors in granulosa cell fate decision ( Smela et al, 2022 ). The differentiated granulosa cell-like cells expressed granulosa cell markers including AMHR2 , CD82 , FOXL2 , FSHR , IGFBP7 , KRT19 , STAR , and WNT4 , and responded to exogenous FSH by producing oestrogen and progesterone ( Smela et al, 2022 ). However, the developmental stage of the in-vitro differentiated pre-GCs is unknown ( Jung et al, 2017 ).…”
Section: Current Progress On In-vitro Differentiat...mentioning
confidence: 99%
“…This represents a big challenge for the isolation of autologous follicular somatic cells to create artificial follicles. An alternative approach could be to differentiate iPSCs from menopausal individuals into granulosa and theca cells in vitro and to subsequently generate transplantable ovarian organoids, but differentiation protocols to obtain both types of somatic ovarian cells in humans are still under development and hence not yet available for clinical applications [72].…”
Section: Hormonal Production and Menopausementioning
confidence: 99%