Abstract:Differentiated embryo chondrocyte 2 (DEC2) is a basic helix-loop-helix-Orange transcription factor that regulates cell differentiation in various mammalian tissues. DEC2 has been shown to suppress the differentiation of mesenchymal stem cells (MSCs) into myocytes and adipocytes. In the present study, we examined the role of DEC2 in the chondrogenic differentiation of human MSCs. The overexpression of DEC2 exerted minimal effects on the proliferation of MSCs in monolayer cultures with the growth medium under un… Show more
“…S5), we assumed that these seven TFs participated in transcriptional regulation of undifferentiated property. Among them, we further focused on Dec2 because previous studies uncovered an inhibitory effect of Dec2 for differentiation-related factors in other types of stem cells 38–40 .Figure 2WGCNA identifies transcription factor network (TFN) modules potentially involved in neonatal germ cell development. ( a ) Five distinct TFN modules were identified by expression correlation analysis.…”
Gonocyte-to-spermatogonia transition is a critical fate determination process to initiate sperm production throughout the lifecycle. However, the molecular dynamics of this process has not been fully elucidated mainly due to the asynchronized differentiation stages of neonatal germ cells. In this study, we employed single cell RNA sequencing analyses of P1.5–5.5 germ cells to clarify the temporal dynamics of gene expression during gonocyte-to-spermatogonia transition. The analyses identified transcriptional modules, one of which regulates spermatogonial gene network in neonatal germ cells. Among them, we identified
Dec2
, a bHLH-type transcription factor, as a transcriptional repressor for a spermatogonial differentiation factor
Sohlh1
. Deficiency of
Dec2
in mice induces significant reduction of undifferentiated spermatogonia, and transplantation assay using
Dec2
-depleted cells also demonstrated the impaired efficiency of engraftment, suggesting its role in maintaining spermatogonial stem cells (SSCs). Collectively, this study revealed the intrinsic role of a new SSC factor
Dec2
, which protects germ cells from inadequate differentiation during neonatal testis development.
“…S5), we assumed that these seven TFs participated in transcriptional regulation of undifferentiated property. Among them, we further focused on Dec2 because previous studies uncovered an inhibitory effect of Dec2 for differentiation-related factors in other types of stem cells 38–40 .Figure 2WGCNA identifies transcription factor network (TFN) modules potentially involved in neonatal germ cell development. ( a ) Five distinct TFN modules were identified by expression correlation analysis.…”
Gonocyte-to-spermatogonia transition is a critical fate determination process to initiate sperm production throughout the lifecycle. However, the molecular dynamics of this process has not been fully elucidated mainly due to the asynchronized differentiation stages of neonatal germ cells. In this study, we employed single cell RNA sequencing analyses of P1.5–5.5 germ cells to clarify the temporal dynamics of gene expression during gonocyte-to-spermatogonia transition. The analyses identified transcriptional modules, one of which regulates spermatogonial gene network in neonatal germ cells. Among them, we identified
Dec2
, a bHLH-type transcription factor, as a transcriptional repressor for a spermatogonial differentiation factor
Sohlh1
. Deficiency of
Dec2
in mice induces significant reduction of undifferentiated spermatogonia, and transplantation assay using
Dec2
-depleted cells also demonstrated the impaired efficiency of engraftment, suggesting its role in maintaining spermatogonial stem cells (SSCs). Collectively, this study revealed the intrinsic role of a new SSC factor
Dec2
, which protects germ cells from inadequate differentiation during neonatal testis development.
“…Total RNA was isolated as described above and cDNA was synthesized using the GeneAmp RNA PCR kit as described previously ( 24 ). Quantitative real-time PCR analysis was performed using an ABI Prism 7900HT Sequence Detection System with the included software (SDS version 2.4; Applied Biosystems; Thermo Fisher Scientific, Inc.,), based on the ΔΔCq method ( 25 ).…”
Dental pulp cells (DPCs) are promising candidates for use as transplantable cells in regenerative medicine. However, ex vivo expansion of these cells typically requires culture media containing fetal bovine serum, which may cause infection and immunological reaction following transplantation. In addition, the proliferation and differentiation of DPCs markedly depend upon serum batches. Therefore, the present study examined whether DPCs could be expanded under serum-free conditions. DPCs obtained from four donors were identified to proliferate actively in the serum-free medium, STK2, when compared with those cells in control medium (Dulbecco's modified Eagle's medium containing 10% serum). The high proliferative potential with STK2 was maintained through multiple successive culture passages. DNA microarray analyses demonstrated that the gene expression profile of DPCs grown in STK2 was similar to that of cells grown in the control medium; however, a number of genes related to cell proliferation, including placental growth factor and inhibin-βE, were upregulated in the STK2 cultures. Following induction of osteogenesis, DPCs grown in STK2 induced alkaline phosphatase activity and calcification at higher levels compared with the control medium cultures, indicating maintenance of differentiation potential in STK2. This serum-free culture system with DPCs may have applications in further experimental studies and as a clinical strategy in regenerative medicine.
“…These seemingly contrasting effects of TWIST1 highlight how the therapeutic targeting of anti‐chondrogenic factors should take into account the temporal, spatial and cell type‐specific effects in different pathophysiological conditions. Differentiated embryo chondrocyte 2 (DEC2) is another member of the helix‐loop‐helix family of transcription factors that was described as negative regulator of proliferation and chondrogenesis in bone marrow hMSCs . Overexpression of DEC2 in bone marrow hMSC pellet cultures inhibited cell proliferation and GAG accumulation …”
“…Differentiated embryo chondrocyte 2 (DEC2) is another member of the helix-loop-helix family of transcription factors that was described as negative regulator of proliferation and chondrogenesis in bone marrow hMSCs. 54 Overexpression of DEC2 in bone marrow hMSC pellet cultures inhibited cell proliferation and GAG accumulation. 54 SLUG/SNAIL2 is a crucial regulator of MSC fate belonging to the Snail family of zinc-finger transcription factors.…”
Section: N T R a C E L L U L A R A N T I -C H O N D R O G E N I C Rmentioning
confidence: 99%
“…54 Overexpression of DEC2 in bone marrow hMSC pellet cultures inhibited cell proliferation and GAG accumulation. 54 SLUG/SNAIL2 is a crucial regulator of MSC fate belonging to the Snail family of zinc-finger transcription factors. SLUG overexpression during chondrogenesis of ATDC5 strongly inhibited collagen II and aggrecan expression.…”
Section: N T R a C E L L U L A R A N T I -C H O N D R O G E N I C Rmentioning
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