KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.

Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat

Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.

Single-cell RNA sequencing reveals Nestin+active neural stem cells outside the central canal after spinal cord injury

Neural stem cells(NSCs)in the spinal cord hold great potential for repair after spinal cord injury(SCI).The ependyma in the central canal(CC)region has been considered as the NSCs source in the spinal cord.However,the ependyma function as NSCs after SCI is still under debate.We used Nestin as a marker to isolate potential NSCs and their immediate progeny,and characterized the cells before and after SCI by single-cell RNA-sequencing(scRNA-seq).We identified two subgroups of NSCs:the subgroup located within the CC cannot prime to active NSCs after SCI,while the subgroup located outside the CC were activated and exhibited the active NSCs properties after SCI.We demonstrated the comprehensive dynamic transcriptome of NSCs from quiescent to active NSCs after SCI.This study reveals that Nestin+cells outside CC were NSCs that activated upon SCI and may thus serve as endogenous NSCs for regenerative treatment of SCI in the future.

BAP60 plays an opposite role to the MRT-NURF complex in regulating lipid droplet size

The lipid droplet(LD)is a unique cellular organelle with a phospholipid monolayer coated with resident proteins.LDs are important for cellular neutral lipid storage and utilization.As spherical balls,LDs accommodate a lot more neutral lipids with a small increase of size.Disrupted LD dynamics,which can be reflected by abnormal LD size alteration,has been linked to many important metabolic diseases,including obesity,neutral lipid storage disease(NLSD).

Mapping Genome-wide Binding Sites of Prox1 in Mouse Cochlea Using the CUT&RUN Approach

Dear Editor,Our auditory organ,the cochlea,resides in the ventral portion of the inner ear,and its sensory epithelium,the organ of Corti,contains hair cells(HCs)and supporting cells(SCs),which are both descendants of the same progenitors.HCs are prone to damage by multiple ototoxic factors,and how to regenerate damaged HCs using key genes involving cochlear development is of importance[1,2].Cochlear progenitor cells express Sox2 and prolif-erate before embryonic day 12.5(E12.5)in the mouse but become quiescent in an apical-to-basal gradient between E12.5 and E14.5[3].