Biology subjects

Singh, H. P.

Publications and source records attributed to Singh, H. P..

4 recordsLinked to original sources

bioRxiv2023

Single cell transcriptomics reveals early photoreceptor trajectories and a cancer-predisposed cone precursor state

Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin, yet the developmental basis for their distinct behaviors is poorly understood. Here, we used deep full-length single-cell RNA-sequencing (scRNA-seq) to distinguish post-mitotic cone and rod developmental states and identify cone-specific features that contribute to retinoblastomagenesis. The analyses revealed nascent, immediately post-mitotic cone- and rod precursor populations characterized by higher THRB or NRL regulon activities, immature and maturing cone and rod precursors with concurrent cone- and rod-related gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Cell-state-specific gene expression features inferred based on full-length scRNA-seq were consistent with past single nucleus 3 RNA-seq analyses. Beyond the cell state characterizations, full-length scRNAseq revealed that both L/M cone and rod precursors co-expressed NRL and THRB RNAs, yet they differentially expressed functionally antagonistic NRL and THRB isoforms and prematurely terminated THRB transcripts. Moreover, early L/M cone precursors exhibited successive expression of several lncRNAs along with MYCN, which composed the seventh most L/M-cone-specific regulon, and SYK, which was implicated in the cone precursors proliferative response to RB1 loss. These findings reveal previously unresolved photoreceptor precursor states and suggest a role for early cone-precursor-intrinsic SYK expression in retinoblastoma initiation. Impact StatementFeatures acquired by early post-mitotic retinal cells underlie the distinct behaviors of rods and the cone cells of origin of retinoblastoma tumors.

developmental biology↗

bioRxiv2022

The role of floral traits in community assembly process at high elevations in Lesser Himalaya

O_LIEcological theory postulates that plant trait research should consider multiple traits related to different organs and/or ontogenetic stages as such traits represent different ecological niche axes. Particularly, floral traits have been suggested to play an important role in assembling plant communities along environmental gradients as they determine the reproductive success, one of the key functions in plants. Yet, the predictive power of floral traits in community assembly research remains largely unverified empirically. C_LIO_LIWe analyzed the predictive power of six floral traits of 139 herbaceous species for inferring community assembly process in twenty-one sites located along an elevation gradient in Lesser Himalaya ranging from 2,000 to 4,000 meters above sea level. The floral trait variability along the gradient was analyzed using community-weighted trait mean (CWM) values and functional diversities (FD) calculated for each of the study communities. C_LIO_LIThe CWM values for onset of flowering and flower display area increased significantly with increasing elevation, whereas specific flower area showed an opposite pattern. In combination with convergence in onset of flowering and specific area (i.e., lower FD values in high elevation sites), these patterns suggest that abiotic filtering and plant-pollinator interactions affected the floral trait composition of the communities studied. Increasing low-temperature stress towards high-elevation sites selected for late-flowering species that produce resource-intensive flowers with larger display areas. C_LIO_LILow pollinator abundancy and activity in high elevation, could also explain why these traits were selected in the study communities. Delayed flowering with increasing elevations might facilitate the phenological overlap of plants and their pollinators, as pollinator activity at higher elevation peaks in the second half of the vegetation period. The dominance of species with low specific flower area and larger display area in high elevation communities were attributed to the increased flower longevity and attraction of pollinators, respectively, to maximize pollination success under pollinator scarcity. C_LIO_LISynthesis. Our study provides empirical support of the recent argument that floral traits contribute considerably to the assembly of plant communities along environmental gradients. Thus, such traits should be included into community assembly research agenda as they represent key growth and survival ecological functions. C_LI

ecology↗

bioRxiv2022

An investigation into the spatiotemporal patterns of the Nymphalid butterfly Vagrans egista sinha (Kollar, )

Vagrans egista sinha (Kollar, [1844]), the Himalayan Vagrant is a subspecies of Nymphalid (Brush-footed) butterflies spread across Asia, whose western limit is in the north-west India. Observations of this subspecies have considerably increased over the past half-a-decade, with a spike in new sightings to the west of their previously known range. This has been considered as a range extension. The current study reports new records of this species from Bilaspur District, Himachal Pradesh, India (which are the first records for the district), through systematic and opportunistic sampling. This raises the question of whether the purported range extension towards the west could instead be a range shift or vagrancy, and whether there is any shift in elevational ranges in the populations across their known range. Questions pertaining to spatial differences in elevational ranges and seasonal variation, across their range, also piqued our curiosity. Using data from academic sources (such as published literature and museum collections), supplemented by data from public participation in scientific research and personal observations, these research questions are addressed. The accuracy of results when using citizen science data is also explored using the same dataset, focused on the impact of method of extraction of coordinates, and elevation derived from it under different scenarios. It was discovered that there has not been a range shift (either longitudinal or latitudinal) and observations dont suggest vagrancy but a case of range extension. Other results indicated that there was no climb of population to higher elevations, no spatial differences in elevational ranges in the populations, or seasonal variation in activities across their range. It was also discovered that the method of data collection by, and extraction from, citizen science databases, can influence the accuracy of the results. Some problems involved in collecting data are discussed, and remedial solutions are suggested.

ecology↗

bioRxiv2018

Developmental-stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors

Most retinoblastomas initiate in response to the inactivation of the RB1 gene and loss of functional RB protein. The tumors may form without additional genomic changes and develop after a pre-malignant retinoma phase. Despite this seemingly straightforward etiology, mouse models have not recapitulated the genetic, cellular, and stage-specific features of human retinoblastoma genesis. For example, whereas human retinoblastomas appear to derive from cone photoreceptor precursors, current mouse models develop tumors that derive from other retinal cell types. To investigate the basis of the human cone-specific oncogenesis, we compared developmental-stage-specific cone precursor responses to RB loss in human and murine retina cultures and in cone-specific Rb1 knockout mice. We report that RB-depleted maturing (ARR3+) but not immature (ARR3-) human cone precursors enter the cell cycle, proliferate, and form retinoblastoma-like lesions characterized by Flexner-Wintersteiner rosettes, then form low or non-proliferative pre-malignant retinoma-like lesions with fleurettes and high p16INK4A and p130 expression, and finally form highly proliferative retinoblastoma-like masses. In contrast, in murine retina, only RB-depleted immature (Arr3-) cone precursors entered the cell cycle and they failed to progress from S to M phase. Moreover, whereas the intrinsically highly expressed MDM2 and MYCN contribute to RB-depleted maturing (ARR3+) human cone precursor proliferation, ectopic MDM2 and Mycn promoted only immature (Arr3-) murine cone precursor cell cycle entry. These findings demonstrate that developmental-stage-specific as well as speciesand cell-type-specific features sensitize to RB1 inactivation and reveal the human cone precursors capacity to model retinoblastoma initiation, proliferation, pre-malignant arrest, and tumor growth.\n\nSignificance StatementRetinoblastoma is a childhood tumor that forms in response to mutations in the RB1 gene and loss of functional RB protein. Prior studies suggested that retinoblastomas arise from cone photoreceptor precursors, whereas mouse models yield tumors deriving from other retinal cell types and lacking human retinoblastoma features. Here, we show that in cultured human retinae, retinoblastomas initiate from RB-depleted cone precursors that are in a specific maturation state and form pre-malignant \"retinomas\" prior to retinoblastoma lesions, as is believed to occur in retinoblastoma patients. In contrast, Rb-deficient mouse cone precursors of similar maturation state and supplemented with human-cone-precursor-specific oncoproteins fail to proliferate. Thus, human species-specific developmental features underlie retinoblastomagenesis and may challenge the production of accurate mouse retinoblastoma models.

cancer biology↗