Biology subjects

Singh, P.

Publications and source records attributed to Singh, P..

At least 199 records · Page 11Linked to original sources

bioRxiv2020

The Nrd1p-Nab3p-Sen1p complex constitutes a vital component of the nuclear mRNA surveillance in Saccharomyces cerevisiae

In all eukaryotes, selective nuclear degradation of aberrant mRNAs by nuclear exosome and its cofactors TRAMP, and CTEXT contribute to the fidelity of the gene expression pipeline. In the model eukaryote, Saccharomyces cerevisiae, the Nrd1p-Nab3p-Sen1p (NNS) complex, previously known to be involved in the transcription termination and matured 3-end formation of vast majority of non-coding and several coding RNAs, is demonstrated to universally participate in the nuclear decay of various kinds of faulty messages in this study. Consistently, nrd1-1/nrd1-2 mutant cells display impairment of the decay of all kinds of aberrant mRNAs, like the yeast mutants deficient in Rrp41p, Rrp6p, and Rrp4p. nrd1{Delta}CID mutation (consisting of Nrd1p lacking its CID domain thereby abrogating its interaction with RNAPII) however, abolishes the decay of aberrant messages generated during early phases of mRNP biogenesis (transcription elongation, splicing and 3-end maturation) without affecting the decay rate of the export-defective mRNAs. Mutation in the 3-end processing factor, Pcf11p, in contrast, displayed a selective abolition of the decay of the aberrant mRNAs, generated at the late phase of mRNP biogenesis (export-defective mRNAs) without influencing the faulty messages spawned in the early phase of mRNP biogenesis. Co-transcriptional recruitment of Nrd1p onto the faulty messages, which relies on RNAPII during transcription elongation and on Pcf11p post transcription, is vital for the exosomal decay of aberrant mRNAs, as Nrd1p deposition on the export-defective messages led to the Rrp6p recruitment and eventually, their decay. Thus, presence of the Nrd1p mark on aberrant mRNAs appears rate-limiting for the distinction of the aberrant messages from their normal functional counterparts. Authors SummaryAberrant/faulty mRNAs generated from the deficiencies in any of the mRNP biogenesis events are promptly eliminated by the nuclear exosome and its cofactors TRAMP and CTEXT complexes. These machineries work relentlessly in the nucleus to detect all kinds of aberrant mRNAs and selectively target them for destruction. However, initial detection of a minuscule amount of aberrant mRNA in the vast background of normal mRNAs is quite challenging and its mechanism remains elusive. In this work, we demonstrate that, the trimeric Nrd1p-Nab3p-Sen1p complex, previously implicated in the transcription termination of diverse non-coding RNAs and a handful of mRNAs, constitute an integral component of the nuclear mRNA surveillance mechanism in bakers yeast Saccharomyces cerevisiae. Major component of this complex, Nrd1p is demonstrated to be recruited selectively onto various classes of representative model aberrant messages either co-transcriptionally by RNA Polymerase II or post-transcriptionally by Pcf11p. Binding of Nrd1p to the export-defective special mRNAs further leads to the recruitment of Rrp6p on to them thereby leading to their degradation. NNS complex thus plays a vital role of initially recognizing the faulty messages and further assists in the recruitment of the nuclear exosome for their prompt elimination.

molecular biology↗

bioRxiv2020

A distinct phylogenetic cluster of Indian SARS-CoV-2 isolates

From an isolated epidemic, COVID-19 has now emerged as a global pandemic. The availability of genomes in the public domain following the epidemic provides a unique opportunity to understand the evolution and spread of the SARS-CoV-2 virus across the globe. The availability of whole genomes from multiple states in India prompted us to analyse the phylogenetic clusters of genomes in India. We performed whole-genome sequencing for 64 genomes making a total of 361 genomes from India, followed by phylogenetic clustering, substitution analysis, and dating of the different phylogenetic clusters of viral genomes. We describe a distinct phylogenetic cluster (Clade I / A3i) of SARS-CoV-2 genomes from India, which encompasses 41% of all genomes sequenced and deposited in the public domain from multiple states in India. Globally 3.5% of genomes, which till date could not be mapped to any distinct known cluster fall in this newly defined clade. The cluster is characterized by a core set of shared genetic variants - C6312A (T2016K), C13730T (A88V/A97V), C23929T, and C28311T (P13L). Further, the cluster is also characterized by a nucleotide substitution rate of 1.4 x 10-3 variants per site per year, lower than the prevalent A2a cluster, and predominantly driven by variants in the E and N genes and relative sparing of the S gene. Epidemiological assessments suggest that the common ancestor emerged in the month of February 2020 and possibly resulted in an outbreak followed by countrywide spread, as evidenced by the low divergence of the genomes from across the country. To the best of our knowledge, this is the first comprehensive study characterizing the distinct and predominant cluster of SARS-CoV-2 in India.

genomics↗

bioRxiv2020

Inhibition of Striatal-Enriched Protein Tyrosine Phosphatase (STEP) Activity Reverses Behavioral Deficits in a Rodent Model of Autism.

Autism spectrum disorders (ASDs) are highly prevalent childhood illnesses characterized by impairments in communication, social behavior, and repetitive behaviors. Studies have found aberrant synaptic plasticity and neuronal connectivity during the early stages of brain development and have suggested that these contribute to an increased risk for ASD. STEP is a protein tyrosine phosphatase that regulates synaptic plasticity and is implicated in several cognitive disorders. Here we test the hypothesis that STEP may contribute to some of the aberrant behaviors present in the VPA-induced mouse model of ASD. In utero VPA exposure of pregnant dams results in autistic-like behavior in the pups, which is associated with a significant increase in the STEP expression in the prefrontal cortex. The elevated STEP protein levels are correlated with increased dephosphorylation of STEP substrates GluN2B, Pyk2 and ERK, suggesting upregulated STEP activity. Moreover, pharmacological inhibition of STEP rescues the sociability, repetitive and abnormal anxiety phenotypes commonly associated with ASD. These data suggest that STEP may play a role in the VPA model of ASD and STEP inhibition may have a potential therapeutic benefit in this model.

neuroscience↗

bioRxiv2020

HSPs, Ubiquitins and Antioxidants aid in Heat Tolerance in Tharparkar Indicine cattle

Transcriptome profiling of Vrindavani and Tharparkar cattle revealed that more numbers of genes dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.5 % of upregulated genes in Vrindavani were downregulated in Tharparkar and 17.5% upregulated genes in Tharparkar were downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naive unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.

physiology↗

bioRxiv2020

Robust range of auditory periphery development, eye opening, and brain gene expression in Wistar rat pups that experience variation in maternal backgrounds

The experience of variation in maternal licking and grooming (LG) is considered a critical influence in neurodevelopment related to stress and cognition, but little is known about its relationship to early sensory development. In this study, we used a maternal selection approach to test the hypothesis that differences in LG during the first week of life influence the timing of hearing onset in Wistar rat pups. We performed a range of tests, including auditory brainstem responses (ABR), tracking of eye opening (EO), micro-CT X-ray tomography, and qRT-PCR to monitor neurodevelopmental changes in the female and male progeny of low-LG and high-LG dams. Our results show that variation in maternal LG is not overtly associated with different timing of ABR onset and EO in the progeny. However, the data provide insight on the delay between hearing onset and EO, on key functional and structural properties that define hearing onset at the auditory periphery, and on changes in brain gene expression that include the first evidence that: a) the hypoxia-sensitive pathway is regulated in subcortical and cortical auditory brain regions before hearing onset, and b) implicates maternal LG in regulation of Bdnf signaling in auditory cortex after hearing onset. Altogether, these findings provide a baseline to evaluate how factors that severely disrupt the early maternal environment may affect the expression of robust developmental sensory programs. SIGNIFICANCE STATEMENTEarly life experience during sensitive developmental periods can induce long-term effects on the neurobiological development of the offspring. In the present work we tested the hypothesis that variation in maternal licking and grooming (LG) affects the timing of hearing onset in Wistar rat pups. To our surprise the results did not support the hypothesis. Instead, we found a robust range of early and late auditory development that was independent of maternal LG. Nevertheless, the study provides new findings on the delay between hearing onset and eye opening, on key functional and structural properties that define hearing onset at the auditory periphery, and the first evidence that a) the hypoxia-sensitive pathway is regulated in the central auditory system during the sensitive period before hearing onset, and b) maternal LG is implicated in regulation of Bdnf signaling during the sensitive period after hearing onset. These findings provide a baseline to evaluate how factors that severely disrupt the early maternal environment may affect the expression of robust developmental sensory programs.

neuroscience↗

bioRxiv2020

Opportunities for prioritizing and expanding conservation enterprise in India using carnivores as flagships

Conservation interventions in developing countries are frequently thwarted by socio-economic agendas, severely limiting the scope and rigor of biodiversity and habitat conservation. Very few ecological assessments incorporate human interests in conservation prioritization, creating asynchrony between planning and implementation. For conservation actions to be logistically feasible, multiple criteria including ecological, social, economic and administrative aspects must be considered. Understanding how these different dimensions interact spatially is also important for gauging the potential for conservation success. Here, we use a guild of select mammalian carnivores (wild canids and hyenas) in India to (i) generate distribution maps at the spatial scale of administrative sub-districts, that is relevant to management, (ii) examine ecological, social and biogeographic factors associated with their distribution, quantify key threats, and identify areas important for their conservation, (iii) use prioritization tools for balancing habitat conservation, human needs and economic growth, and (iv) evaluate the spatial congruence between areas with high conservation potential, and areas currently in focus for protection efforts, conservation investments, and infrastructure development. We find that the current Protected Area system does not adequately cover or represent diverse habitats, that there is immense potential for States to increase financial investments towards alternative conservation strategies, and, most infrastructure projects may be jeopardizing important carnivore habitats. Our framework allowed for identifying locations where conservation investments would lead to the highest dividends for flagship carnivores and associated species across habitats. We make a case for re-evaluating how large-scale prioritization assessments are made, and for broadening the purview of conservation policies in India and other developing countries.

ecology↗

bioRxiv2019

Successful mating and hybridisation in two closely related flatworm species despite significant differences in reproductive morphology and behaviour

Speciation is usually a gradual process, in which reproductive barriers between two species accumulate over time. Reproductive traits, like genital morphology and mating behaviour, are some of the fastest diverging characters and can serve as reproductive barriers. The free-living flatworm Macrostomum lignano, an established model for studying sex in hermaphrodites, and its congener M. janickei are closely related, but differ substantially in their male intromittent organ (stylet) morphology. Here, we examine whether these morphological differences are accompanied by differences in behavioural traits, and whether these could represent barriers to successful mating and hybridization between the two species. Our data shows that the two species differ in many aspects of their mating behaviour, with M. janickei having a five-fold longer copulation duration, copulating less frequently, and having a longer and more delayed suck behaviour (a postcopulatory behaviour likely involved in sexual conflict). Interestingly, and despite these significant morphological and behavioural differences, the two species mate readily with each other in heterospecific pairings, often showing behaviours of intermediate duration. Although both species have similar fecundity in conspecific pairings, the heterospecific pairings revealed clear postmating barriers, as only few heterospecific pairings produced F1 hybrids. These hybrids had a stylet morphology that was intermediate between that of the parental species, and they could successfully backcross to both parental species. Finally, in a mate choice experiment we tested if the worms preferentially mated with conspecifics over heterospecifics, since such a preference could represent a premating barrier. Interestingly, the experiment showed that the nearly two-fold higher mating rate of M. lignano caused it to mate more with conspecifics, leading to assortative mating, while M. janickei ended up mating more with heterospecifics. Thus, while the two species can hybridize, the mating rate differences could possibly lead to higher fitness costs for M. janickei compared to M. lignano.

animal behavior and cognition↗

bioRxiv2019

Microscaled Proteogenomic Methods for Precision Oncology

Cancer proteogenomics integrates genomics, transcriptomics and mass spectrometry (MS)-based proteomics to gain insights into cancer biology and treatment efficacy. A proteogenomics approach was therefore developed for frozen core biopsies using tissue-sparing specimen processing with a \"microscaled\" proteomics workflow. For technical proof-of-principle, biopsies from ERBB2 positive breast cancers before and 48-72 hours after the first dose of neoadjuvant trastuzumab-based chemotherapy were analyzed. ERBB2 protein and phosphosite levels, as well as mTOR target phosphosites, were significantly more suppressed upon treatment in cases associated with pathological complete response, suggesting MS-based pharmacodynamics is achievable. Furthermore, integrated analyses indicated potential causes of treatment resistance including the absence of ERBB2 amplification (false-ERBB2 positive) and insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification (pseudo-ERBB2 positive). Candidate resistance features in true-ERBB2+ cases, including androgen receptor signaling, mucin expression and an inactive immune microenvironment were observed. Thus, proteogenomic analysis of needle core biopsies is feasible and clinical utility should be investigated.

cancer biology↗

bioRxiv2019

Complex multi-trait responses to multivariate environmental cues in a seasonal butterfly

Developmental plasticity in a seasonal environment allows an organism to optimally match its life-history traits with the fluctuating conditions. This critically relies on abiotic and biotic factors, such as temperature or food quality, that act as environmental cues and predict seasonal transitions. In most seasonal environments, multiple factors vary together, making it crucial to understand their combined effects on an organisms phenotype. Here, we study plasticity in a multivariate environment in the butterfly Bicyclus anynana that exhibits two distinct seasonal phenotypes. Temperature is an important cue mediating plasticity in this species, but other environmental cues such as larval host plant quality could also be informative since plant quality deteriorates during the transition from wet to dry season in the field. We examine how temperature and host plant quality interact to affect life-history traits. Using a full-factorial design, we expose cohorts of larvae to either poor (old plants) or high (young plants) quality plants at different temperatures. Our results show that plant quality had a temperature and sex-dependent effect on life-history traits. At lower and intermediate temperatures, it decreased body mass and prolonged development time, indicating that poor plant quality acted as a stressor. However, metabolic rates in adults were not affected, indicating that individuals could, at least in part, compensate for stressful juvenile conditions. In contrast, at higher temperatures poor plant quality induced a partial dry-season phenotype, indicating that it may have acted as an environmental cue. Moreover, poor plant quality, particularly in males, also decreased the correlation between life history traits, signifying disrupted phenotypic integration. Our study reveals complex interactive effects of two environmental variables on seasonal plasticity, reflecting differences in their reliability as seasonal cues. This highlights the importance of studying the combined effects of multiple environmental factors to better understand the regulation of phenotypic plasticity in wild.

ecology↗

bioRxiv2019

Higher order interactions and coexistence theory

Higher order interactions (HOIs) have been suggested to stabilize diverse ecological communities. However, their role in maintaining species coexistence from the perspective of modern coexistence theory is unknown. Here, using a three-species Lotka-Volterra model, we derive a general rule for species coexistence modulated by HOIs. We show that negative HOIs that intensify pairwise competition, can promote coexistence across a wide range of fitness differences, provided that HOIs strengthen intraspecific competition more than interspecific competition. In contrast, positive HOIs that alleviate pairwise competition can also stabilize coexistence across a wide range of fitness differences, irrespective of differences in strength of inter- and intraspecific competition. Furthermore, we extend our three-species analytical result to multispecies competitive community and show, using simulations, that feasible multispecies coexistence is possible provided that strength of negative intraspecific HOIs is higher than interspecific HOIs. In addition, multispecies communities, however, become unstable with positive HOIs as such higher-order interactions could lead to disproportionately infeasible growth rates. This work provides crucial insights on the underlying mechanisms that could maintain species diversity and links HOIs with modern coexistence theory.

ecology↗

bioRxiv2019

Ki-67 supports global gene expression programmes driving tumourigenesis

Recent studies have shown that the cell proliferation antigen Ki-67 is not required for cell proliferation. Here, we demonstrate that Ki-67 enables implementation of transcriptional programmes conferring cellular plasticity, and is required for each step of tumour initiation, growth and metastasis. Ki-67 knockout causes global transcriptome remodelling, which, in mammary carcinoma cells, inhibits the epithelial-mesenchymal transition in a polycomb-repressive complex 2-dependent manner. This results in suppression of stem cell characteristics and sensitisation to various drug classes. Cancer cells lacking Ki-67 proliferate normally in vivo, but tumour growth is inhibited due to disrupted angiogenesis, and metastasis is abrogated. Finally, mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumourigenesis. Thus, Ki-67, which is expressed in all proliferating cancer cells, confers the plasticity required for different steps of carcinogenesis.

cancer biology↗

bioRxiv2019

A chromosome-scale assembly of allotetraploid Brassica juncea (AABB) elucidates comparative architecture of the A and B genomes

Brassica juncea (AABB; genome size [~]920 Mb), commonly referred to as mustard, is a natural allopolyploid of two diploid species - B. rapa (AA) and B. nigra (BB). We report a highly contiguous genome assembly of an oleiferous type of B. juncea variety Varuna, an archetypical Indian gene pool line of mustard, with [~]100x PacBio single-molecule real-time (SMRT) reads providing contigs with an N50 value of >5Mb. Assembled contigs were corrected and scaffolded with BioNano optical mapping. Three different linkage maps containing a large number of GBS markers were developed and used to anchor scaffolds/contigs to the 18 linkage groups of B. juncea. The resulting chromosome-scale assembly is a significant improvement over the previous draft assembly of B. juncea Tumida, a vegetable type of mustard. The assembled genome was characterized for transposons, centromeric repeats, gene content, and gene block associations. Both A and B genomes contain highly fragmented gene block arrangements. In comparison to the A genome, the B genome contains a significantly higher content of LTR/Gypsy retrotransposons, distinct centromeric repeats and a large number of B. nigra specific gene clusters that break the gene collinearity between the A and the B genomes. The genome assembly reported here will provide a fillip to the breeding work on oleiferous types of mustard that are grown extensively in the dry land areas of South Asia and elsewhere.

genomics↗

bioRxiv2019

CX3CL1 binding protein-2 (CBP2) of Plasmodium falciparum binds nucleic acids

Several exported Plasmodium falciparum(Pf) proteins contribute to malaria biology through their involvement in cytoadherence, immune evasion and host cell remodelling. Many of these exported proteins and other host molecules are present in iRBC (infected red blood cell) generated extracellular vesicles (EVs), which are responsible for host cell modification and parasite development. CX3CL1 binding proteins (CBPs) present on the surface of iRBC have been reported to contribute to cytoadhesion by binding with the chemokine CX3CL1 via their extracellular domains. Here, we have characterized the cytoplasmic domain of CBP2to understand its function in parasite biology using biochemical and biophysical methods. Recombinant cytoplasmic CBP2 (rcCBP2) binds nucleic acids showing interaction with DNA/RNA. rcCBP2 shows dimer formation under non-reducing conditions highlighting the role of disulphide bonds in oligomerization while ATP binding leads to structural changes in the protein. In vitro interaction studies depict its binding with a Maurers cleft resident protein PfSBP1, which is influenced by ATP binding of rcCBP2. Our results suggest CBP2 as a two-transmembrane (2TM) receptor responsible for targeting EVs and delivering cargo to host endothelial cells. We propose CBP2 as an important molecule having roles in cytoadherence and immune modulation through its extracellular and cytoplasmic domains respectively.

molecular biology↗

bioRxiv2019

High-throughput propagation of human prostate tissue from induced-pluripotent stem cells

Primary culture of human prostate organoids is slow, inefficient and laborious. To overcome this, we demonstrate a new high-throughput model where rapidly proliferating and easily handled induced pluripotent stem cells, for the first time, enable generation of human prostate tissue in vivo and in vitro. Using a co-culture technique with urogenital sinus mesenchyme, we recapitulated the in situ prostate histology, including the stromal compartment and the full spectrum of epithelial differentiation. This approach overcomes major limitations in primary cultures of human prostate stem, luminal and neuroendocrine cells, as well as the stromal microenvironment. These models provide new opportunities to study prostate development, homeostasis and disease.

developmental biology↗

bioRxiv2019

Basal ganglia contributions during the learning of a visuomotor rotation: effect of dopamine, deep brain stimulation and reinforcement

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinsons disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results suggest that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.

neuroscience↗

bioRxiv2019

CDK2 kinase activity is a regulator of male germ cell fate

The ability of men to remain fertile throughout their lives depends upon establishment of a spermatogonial stem cell (SSC) pool from gonocyte progenitors, and also maintaining the proper balance between SSC renewal and spermatogenic differentiation throughout life. Depletion of SSCs causes infertility with a Sertoli Cell Only Syndrome (SCOS) phenotype. We previously created a mouse strain in which an inhibitory phosphorylation site (Tyr15) of Cyclin-dependent kinase 2 (Cdk2) was altered. Juvenile males homozygous for this allele (Cdk2Y15S) initiate the first round of spermatogenesis, which originates from prospermatogonia, but meiocytes arrest due to chromosomal defects resembling those in Cdk2-/- mice. Subsequent waves of spermatogonial differentiation and meiosis were largely absent, leading to an SCOS-like phenotype. Here, we demonstrate that Cdk2Y15S/Y15S mice possess mitotically active GFRa1+ SSC-like cells, but they are impaired in their ability to differentiate. Marker analysis and single cell RNA-seq revealed defective differentiation of gonocytes into SSCs. Biochemical and genetic data demonstrated that Cdk2Y15S is a gain-of-function allele causing deregulated kinase activity, and its phenotypic effects could be reversed by mutating the Thr160 positive regulatory site in cis. These results demonstrate that precise temporal regulation of CDK2 activity in male germ cell development and in the cell cycle is critical for long-term spermatogenic homeostasis.

genetics↗

bioRxiv2019

Genome-wide expression analysis identifies core components during iron starvation in hexaploid wheat

Iron is one of essential micronutrient for all organisms. Its deficiency causes a severe loss in crops yield. Nevertheless, our current understanding on major crops response to Fe deficiency remains limited. Herein, we investigated the effect of Fe deprivation at both transcriptomic and metabolic levels in hexaploid wheat. A genome-wide gene expression reprogramming was observed with a total of 5854 genes showing differential expression in roots of wheat subjected to Fe-starved medium. Subsequent, analysis revealed a predominance of strategy-II mode of Fe uptake, with induced genome bias contribution from the A and B genomes. In general, the predominance of genes encoding for nicotianamine synthase, yellow stripe like transporters, metal transporters, ABC transporters and zinc-induced facilitator-like protein was noticed. Our transcriptomic data were in agreement with the GC-MS analysis that showed an enhancement of accumulation of various metabolites such as fumarate, malonate, succinate and xylofuranose, which could be linked for enhancing Fe-mobilization. Interestingly, Fe starvation causes a significant temporal increase of glutathione-S-transferase both at transcriptional and enzymatic activity, which indicate the important role of glutathione in the response to Fe starvation in wheat roots. Taken together, our result provides new insight on wheat response to Fe starvation and lays foundation to design strategies to improve Fe nutrition in crops.

plant biology↗

bioRxiv2018

Rat bone marrow derived mesenchymal stem cells differentiate to germ cell like cells

Summary StatementThe in vitro differentiation of rMSCs provides an excellent model for studying cell commitment and their potential in stem cell technology. We have demonstrated that rat bone marrow derived MSCs are able to differentiate into germ-line cells in vitro which has an enormous scope in the advancement of fertility research. In future, this technique can be utilized in different domestic animal species for propagation of elite germ plasm.\n\nAbstractGerm cells undergo distinctive male or female pathways to produce spermatozoa or oocyte respectively essential for sexual reproduction. Mesenchymal stem cells (MSCs) have the capacity of trans-differentiation to form the multiple lineages of cells of mesoderm, endoderm, and ectoderm origin. Herein, MSCs were isolated from rat bone marrow and characterized by their morphological features, expression of surface markers by immunophenotyping and molecular biology tools as well as self renewal and differentiation capability. Thereafter, by inducing these cells with retinoic acid we could able to show that bone marrow derived MSCs are able to trans-differentiate into male germ cell-like cells which were further characterized by the expressions of germ cell specific markers. This in vitro study for the generation of germ-like cells suggests that bone marrow MSCs can be a potential source of germ cells that could be a sustainable source of sperm / oocyte production for potential therapeutic applications in future. Moreover, this technique can be applied in different domestic animal species for propagation of elite germ plasm.

cell biology↗